Bolton_et_al._Supplement

SUPPLEMENTAL RESULTS AND DISCUSSION

Some HPr-1AR ARE-containing Genes Are Unresponsive to Androgen

Intracellular receptors specify complex patterns of gene expression that are cell and gene specific. For example, among the 62 androgen non-responsive genes in HPr-1AR that nevertheless bear AR-occupied intragenic AREs in those cells, seven are androgen regulated in

LNCaP cells (DePrimo et al. 2002; Nelson et al. 2002). In general, it seems likely that many of these AR binding sites may confer androgen responses in different cellular contexts, reflecting, for example, requirements for additional coregulators to enable hormonal control. Thus, for this subset of genes, AR occupancy is not the primary determinant for AR regulation. Alternatively, some of these AR-occupied genes may be strongly expressed prior to androgen treatment, rendering their induction difficult to measure. However, our qPCR expression data do not support this alternative.

ARBRs Function as AREs in Androgen-Mediated Transcriptional Regulation

Interestingly, four of the 500-bp ARBRs identified near repressed ARGs produced activation rather than repression of luciferase expression when tested in reporter contexts, whereas three failed to confer androgen regulation in either direction (ECB and KRY, unpublished). Although we do not yet understand this regulatory “polarity reversal”, our result is similar to earlier findings in which “negative” glucocortoicoid response elements direct transcriptional activation in simple contexts (M. Cronin and KRY, unpublished); thus, the mechanisms of transcriptional repression may prove to be more complex than induction, perhaps requiring components of chromatin structure or additional regulatory factors that fail to function in the reporter context.

1 Bolton_et_al._Supplement

SUPPLEMENTAL MATERIALS AND METHODS

Expression Microarray Analysis

We identified androgen-regulated transcripts by converting RNA from vehicle or androgen- treated HPr-1AR cells into double-stranded cDNA, and hybridizing to spotted cDNA microarrays comprised of at least 10,865 predicted protein-coding genes and 3,035 expressed sequence tags. Total RNA was isolated from HPr-1AR cells with QIAshredder and RNeasy Mini kits (Qiagen). Microarray analysis was performed as described (Fox et al. 2003). In brief, RNA was linearly amplified through two rounds of in vitro transcription (Baugh et al. 2001) and coupled to N-hydroxysuccunimidyl esters of Cy3 or Cy5 (Amersham) (Hughes et al. 2001). For printing the arrays, DNA was prepared by colony-PCR (Bohlander et al. 1992) of the sequence verified Research Genetics cDNA library sets containing 21,632 clones. Primary data were analyzed using GENEPIX 3.0 software (Axon Instruments) and normalized by NOMAD

(http://ucsf-nomad.sourceforge.net). The ratio-of-medians values were log-transformed and differentially expressed genes were identified using Significance Analysis of Microarrays (SAM) analysis with a q-value cutoff < 4.2% (Tusher et al. 2001).

DNase I Hypersensitive Site Mapping

The procedure was adapted from previous protocols (Zaret and Yamamoto 1984; Cleutjens et al.

1997). Briefly, HPr-1AR cells treated with vehicle or R1881 for 4 hr were cooled to 4°C,

harvested by scraping in DNase I buffer (20 mM HEPES-KOH, pH 7.4, 3 mM MgCl2, 0.5 mM

CaCl2, 5% glycerol, 0.2 mM spermine, 0.2 mM spermidine, supplemented with protease inhibitors) and disrupted in a Dounce homogenizer. Ten A260 units of nuclei in DNase I buffer

2 Bolton_et_al._Supplement were treated with 20 Kunitz units/ml of DNAse I (Qiagen) for 0, 0.5, 1,2,3,4,6 or 8 min at room temperature. The DNase digestion was stopped with an equal volume of 2x Stop buffer (50 mM

Tris-HCl, pH 8; 5 mM EDTA; 200 mM NaCl and 200 µg/ml Proteinase K) and incubated for 1 hr at 55°C. The DNA fragments were purified using QIAquick PCR Purification kit (Qiagen) and digested with Xba I. DNA fragments were fractionated by agarose gel electrophoresis, transferred to Hybond-N+ filters (Amersham) and fixed by UV crosslinking. Membrane-bound

DNAs were hybridized to an SGK promoter-specific DNA probe (-375 to +544 relative to the transcription start site) that was internally labeled and purified over G25 Sephadex spin columns.

Hybridization was measured using a Molecular Dynamics PhosphorImager.

Computational Analysis

Similar motifs were clustered using CAST (Ben-Dor et al. 1999; Li et al. 2002; Patil et al. 2004).

The P values of enrichment were calculated from the number of occurrences of each motif

within the 524 ARBRs (Nobs) and the expected number of occurrences (Nexp). Nexp was calculated from its frequency of occurrence within background sequences (200 randomly sampled 100-kb

ChIP-chip regions). The Poisson distribution was then used to calculate the probability of

observing the number of occurrences ≥ Nobs by chance given the expected number of occurrences

Nexp. These P values were then Bonferroni corrected by the number of tests (Patil et al. 2004).

3 Bolton_et_al._Supplement

SUPPLEMENTAL TABLES

Supplemental Table 1. The putative AR binding peaks detected by Mpeak for duplicate independent experiments, resulting in 524 AR binding regions (ARBRs) for HPr-1AR Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr1:6205301-6305301 chr1:6253985-6254035 3.1267 chr1:6253985-6254035 2.8205 6254010 1.01 chr1:6277021-6277071 1.3378 chr1:6288888-6288938 2.7649 chr1:6289485-6289535 2.6236 chr1:6289538-6289588 2.6882 6289537 1.02 chr1:6547195-6647195 chr1:6582471-6582521 1.2674 chr1:6585714-6585764 2.3387 chr1:6585661-6585711 1.6361 6585713 1.03 chr1:6594809-6594859 1.7126 chr1:6615966-6616016 1.5021 chr1:16177870-16277870 chr1:23581591-23681591 chr1:23607642-23607692 3.1094 chr1:23680719-23680769 1.7228 chr1:23680878-23680928 1.5661 23680824 1.04 chr1:29278977-29378977 chr1:32850360-32950360 chr1:32914864-32914914 1.3549 chr1:41569390-41669390 chr1:41600899-41600949 2.5646 chr1:41600899-41600949 2.7303 41600924 1.05 chr1:41623117-41623167 1.4250 chr1:41633414-41633464 1.9657 chr1:41633361-41633411 1.9050 41633413 1.06 chr1:41633838-41633888 1.7977 chr1:41635408-41635458 2.5735 chr1:41635779-41635829 3.2329 chr1:41635779-41635829 2.8095 41635804 1.07 chr1:46468409-46568409 chr1:46518804-46518854 1.8402 chr1:46519607-46519657 2.3492 chr1:46926761-47026761 chr1:46927693-46927743 2.4370 chr1:46927693-46927743 3.0594 46927718 1.08 chr1:46935128-46935178 1.7578 chr1:46935499-46935549 1.7719 chr1:46984587-46984637 3.2702 chr1:46984481-46984531 3.5516 46984559 1.09 chr1:46985070-46985120 1.9752 chr1:46985229-46985279 1.8889 46985175 1.10 chr1:46997825-46997875 1.3461 chr1:55014926-55114926 chr1:55052978-55053028 2.4988 chr1:55052978-55053028 2.1344 Yes 55053003 1.11 chr1:55061339-55061389 1.5554 chr1:55061339-55061389 2.2130 Yes 55061364 1.12 chr1:55105456-55105506 2.0910 chr1:58911806-59011806 chr1:58946248-58946298 2.2190 chr1:58959343-58959393 1.9244 chr1:58963477-58963527 1.7674 chr1:58963477-58963527 2.3196 58963502 1.13 chr1:59002804-59002854 1.7687 chr1:65920884-66020884 chr1:78045828-78145828 chr1:78052676-78052726 2.1833 chr1:78052623-78052673 2.2000 78052675 1.14 chr1:84818201-84918201 chr1:84866414-84866464 3.7892 chr1:84866467-84866517 3.7788 Yes 84866466 1.15 chr1:85708480-85808480 chr1:85715753-85715803 1.6689 chr1:85806989-85807039 1.5336 chr1:85806936-85806986 1.4157 85806988 1.16 chr1:92013676-92113676 chr1:94669336-94769336 chr1:94721989-94722039 1.7732 chr1:94729539-94729589 3.9766 chr1:94729698-94729748 3.9257 94729644 1.17 chr1:94730074-94730124 3.1268 chr1:94731038-94731088 2.3926 chr1:113160847-113260847 chr1:116577877-116677877 chr1:116584318-116584368 2.0176 chr1:116584159-116584209 1.9252 116584264 1.18 chr1:116585013-116585063 3.5620 chr1:116585066-116585116 3.3979 116585065 1.19 chr1:116589226-116589276 1.5016 chr1:116629803-116629853 1.7711 chr1:116631205-116631255 4.0244 chr1:116631292-116631342 3.2328 116631274 1.20 chr1:116632881-116632931 2.6574 chr1:116635630-116635680 1.6490 chr1:116642858-116642908 2.4223 chr1:116642975-116643025 3.0361 116642942 1.21 chr1:142380067-142615067 chr1:142472089-142472139 3.1179 chr1:142472407-142472457 2.8853 142472273 1.22 chr1:142586124-142586174 3.1253 chr1:147795123-147895123 chr1:147841007-147841057 1.9187 chr1:151140741-151254741 chr1:151200154-151200204 2.5446 chr1:151200207-151200257 1.9806 Yes 151200206 1.23 chr1:151203890-151203940 1.9899 chr1:151203890-151203940 2.1120 Yes 151203915 1.24 chr1:151671562-152041562 chr1:151697622-151697672 2.8655 chr1:151723198-151723248 2.8218 chr1:151723145-151723195 3.0027 Yes 151723197 1.25 chr1:151729172-151729222 4.3135 chr1:151756822-151756872 2.0705 chr1:151756928-151756978 2.7010 Yes 151756900 1.26 chr1:151791274-151791324 1.3867 chr1:151802784-151802834 1.8998 chr1:151808602-151808652 3.6921 chr1:151808496-151808546 2.9280 Yes 151808574 1.27 chr1:151820339-151820389 3.8045 chr1:151820233-151820283 3.4778 Yes 151820311 1.28 chr1:151824453-151824503 4.4061 chr1:151824559-151824609 3.3467 Yes 151824531 1.29 chr1:151835344-151835394 2.1675 chr1:151854236-151854286 2.0203 chr1:151854236-151854286 3.0808 Yes 151854261 1.30 chr1:151863719-151863769 3.1661 chr1:151863772-151863822 2.7226 Yes 151863771 1.31 chr1:151865137-151865187 1.3468 chr1:151870669-151870719 2.5251 chr1:151870760-151870810 2.9078 Yes 151870740 1.32 chr1:151916996-151917046 3.3198 chr1:151916996-151917046 3.1002 Yes 151917021 1.33 chr1:151976759-151976809 2.1210 chr1:151981350-151981400 0.8543 chr1:151993365-151993415 2.2438 chr1:151995885-151995935 2.5047 chr1:151998653-151998703 3.6776 chr1:151998653-151998703 2.9638 Yes 151998678 1.34 chr1:152000087-152000137 1.7684 chr1:152010840-152010890 3.8408 chr1:152010840-152010890 3.0054 Yes 152010865 1.35 chr1:152016236-152016286 2.0762

4 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr1:152017518-152017568 1.5430 chr1:152019320-152019370 3.7436 chr1:152019373-152019423 2.8797 Yes 152019372 1.36 chr1:152021380-152021430 1.5838 chr1:152028002-152028052 2.9225 chr1:152028002-152028052 1.9339 Yes 152028027 1.37 chr1:159212980-159312980 chr1:159243123-159243173 2.1204 chr1:159243017-159243067 3.3032 159243095 1.38 chr1:162478547-162662547 chr1:162524913-162524963 3.4737 chr1:162524807-162524857 1.9532 162524885 1.39 chr1:162543663-162543713 2.2175 chr1:162543610-162543660 2.1223 162543662 1.40 chr1:16260927-16260977 2.8860 chr1:166136899-166236899 chr1:166187010-166187060 3.3187 chr1:166186851-166186901 3.1177 Yes 166186956 1.41 chr1:166228681-166228731 1.5356 chr1:170810311-170910311 chr1:171650227-171750227 chr1:183331213-183431213 chr1:189459827-189559827 chr1:189469339-189469389 1.9059 chr1:189510592-189510642 1.9024 chr1:189536097-189536147 3.5040 chr1:189536097-189536147 3.3907 189536122 1.42 chr1:189547982-189548032 2.3981 chr1:193851329-193951329 chr1:198050326-198150326 chr1:198054163-198054213 1.3697 chr1:198055956-198056006 3.1083 chr1:198056568-198056618 3.9796 chr1:198056568-198056618 1.5261 198056593 1.43 chr1:198056939-198056989 2.7958 chr1:198059494-198059544 2.9691 chr1:198059441-198059491 3.2990 198059493 1.44 chr1:198069448-198069498 2.6252 chr1:198084451-198084501 2.3507 chr1:198150012-198150062 1.8799 chr1:198150012-198150062 1.7362 198150037 1.45 chr1:200802679-200902679 chr1:200826864-200826914 1.6463 chr1:200827341-200827391 3.3754 chr1:200827394-200827444 2.8981 200827393 1.46 chr1:200846391-200846441 2.9720 chr1:200846338-200846388 2.6897 200846390 1.47 chr1:200850987-200851037 2.9989 chr1:200850987-200851037 2.8100 Yes 200851012 1.48 chr1:200855504-200855554 2.4026 chr1:203196683-203296683 chr1:203254867-203254917 1.6987 chr1:203262521-203262571 1.6651 Yes 203262546 1.49 chr1:203265661-203265711 2.1903 chr1:203266626-203266676 3.5572 chr1:203266626-203266676 3.3705 203266651 1.50 chr1:203292386-203292436 4.6018 chr1:203292386-203292436 3.6674 203292411 1.51 chr1:203292757-203292807 3.5964 chr1:208090494-208190494 chr1:208091256-208091306 3.7400 chr1:208091256-208091306 2.9083 Yes 208091281 1.52 chr1:208092149-208092199 3.8733 chr1:208092149-208092199 2.8681 208092174 1.53 chr1:208099322-208099372 1.8636 chr1:208145615-208145665 3.3790 No chr1:214858262-214958262 chr1:223315694-223415694 chr1:223373060-223373110 0.9526 chr1:225127603-225227603 chr1:225212723-225212773 2.4632 chr1:225212405-225212455 1.5277 225212589 1.54 chr1:231002006-231102006 chr1:231007176-231007226 1.5355 chr1:231032120-231032170 1.5332 chr1:231045257-231045307 1.9794 chr1:231045204-231045254 2.1125 231045256 1.55 chr1:239664664-239764664 chr2:1606000-1771000 chr2:1606116-1606166 2.8926 chr2:1606232-1606282 2.8108 1606199 2.01 chr2:1606756-1606806 3.3929 chr2:1606597-1606647 2.6352 1606702 2.02 chr2:1650981-1651031 2.8714 chr2:1651151-1651201 2.6705 1651091 2.03 chr2:1655082-1655132 2.1426 Yes 1655107 2.04 chr2:1660003-1660053 1.4143 chr2:1679471-1679521 3.6939 chr2:1679471-1679521 2.5700 1679496 2.05 chr2:1681989-1682039 2.5190 chr2:1682837-1682887 2.3596 chr2:1682837-1682887 2.2656 1682862 2.06 chr2:1725183-1725233 1.2081 Yes 1725208 2.07 chr2:6013000-6113000 chr2:8722710-8822710 chr2:9992419-10093419 chr2:10045313-10045363 2.1976 chr2:10061612-10061662 2.7751 chr2:10063293-10063343 1.7035 chr2:10071881-10071931 1.4234 chr2:37760977-37860977 chr2:37794455-37794505 2.0100 chr2:37794455-37794505 1.8655 37794480 2.08 chr2:37795980-37796030 1.6981 chr2:37814948-37814998 2.5895 chr2:40519095-40619095 chr2:40553114-40553164 2.6500 chr2:61155013-61255013 chr2:64742697-64842697 chr2:64771823-64771873 1.3435 chr2:64776052-64776102 2.1517 chr2:64776417-64776467 1.4620 64776260 2.09 chr2:71219098-71319098 chr2:71224673-71224723 1.5042 chr2:71259396-71259446 2.8765 chr2:71259343-71259393 1.8080 No chr2:71268613-71268663 4.8809 chr2:71268560-71268610 3.8569 Yes 71268612 2.10 chr2:86530100-86630100 chr2:86579843-86579893 2.4151 chr2:86579843-86579893 2.0154 86579868 2.11 chr2:96183053-96283053 chr2:100845130-100945130 chr2:100855886-100855936 2.9647 chr2:100861424-100861474 3.4239 chr2:100861310-100861360 3.8315 100861392 2.12 chr2:100931817-100931867 3.2764 chr2:100931711-100931761 2.9442 100931789 2.13 chr2:100932860-100932910 1.5851 chr2:102644683-102744683 chr2:102661211-102661261 1.7830 chr2:102693985-102694035 3.5066 chr2:102693985-102694035 2.3547 102694010 2.14 chr2:119860694-119960694 chr2:119900159-119900209 3.7705 chr2:119899894-119899944 2.8406 Yes 119900052 2.15 chr2:119908054-119908104 3.0531 chr2:119908054-119908104 2.0394 Yes 119908079 2.16 chr2:119910163-119910213 3.0487 Yes 119910188 2.17 chr2:121216088-121316088 chr2:121257469-121257519 1.5508 chr2:121257416-121257466 1.0504 121257468 2.18 chr2:121265931-121265981 2.0523 chr2:127521094-127631094 chr2:127554993-127555043 2.4437 chr2:127554993-127555043 1.8789 127555018 2.19 chr2:127559107-127559157 1.8654

5 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr2:127564034-127564084 0.9673 chr2:157959654-158059654 chr2:162706559-162806559 chr2:162757341-162757391 1.5574 chr2:162775155-162775205 1.9065 chr2:162774936-162774986 1.8475 162775071 2.20 chr2:162785523-162785573 2.4416 chr2:162785523-162785573 2.0643 162785548 2.21 chr2:162790984-162791034 1.9234 chr2:162794770-162794820 1.4453 chr2:162794717-162794767 1.5898 162794769 2.22 chr2:169088341-169278341 chr2:169104118-169104168 2.4422 Yes 169104143 2.23 chr2:169114064-169114114 2.6131 Yes 169114089 2.24 chr2:169132298-169132348 3.0395 Yes 169132323 2.25 chr2:169164386-169164436 3.4165 chr2:169164492-169164542 2.4694 169164464 2.26 chr2:169165688-169165738 2.2796 chr2:169197670-169197720 4.1427 chr2:169197832-169197882 3.3161 169197776 2.27 chr2:169208859-169208909 1.7541 chr2:169208859-169208909 2.4736 169208884 2.28 chr2:169227964-169228014 3.4387 chr2:169227858-169227908 3.0744 169227936 2.29 chr2:169246857-169246907 2.9153 chr2:169246857-169246907 3.0142 169246882 2.30 chr2:171448706-171548706 chr2:174888872-174988872 chr2:190702961-190802961 chr2:190983940-191083940 chr2:191033697-191033747 2.4868 chr2:191033697-191033747 2.5357 Yes 191033722 2.31 chr2:192487487-192587487 chr2:192537300-192537350 2.1231 chr2:192537472-192537522 3.0101 Yes 192537411 2.32 chr2:192557355-192557405 2.3132 chr2:192557408-192557458 2.7796 Yes 192557407 2.33 chr2:192568357-192568407 2.9058 chr2:192568357-192568407 2.0058 192568382 2.34 chr2:216050297-216176297 chr2:216123520-216123570 3.6904 chr2:216123626-216123676 1.9428 216123598 2.35 chr2:216151126-216151176 2.0713 chr2:216152594-216152644 3.0817 chr2:218910720-219037720 chr2:218963223-218963273 1.8504 chr2:219029947-219029997 2.3843 chr2:228454074-228554074 chr2:228507343-228507393 1.7989 chr2:228508422-228508472 2.6437 chr2:228508422-228508472 2.4487 228508447 2.36 chr2:230354776-230454776 chr2:230363562-230363612 2.6539 chr2:230363921-230363971 1.8532 230363767 2.37 chr2:230365185-230365235 2.4895 chr2:230365185-230365235 1.6592 230365210 2.38 chr2:230369969-230370019 1.8734 chr2:233096369-233196369 chr2:235137693-235237693 chr2:235142785-235142835 1.4724 chr2:235155048-235155098 2.0071 chr2:235155048-235155098 2.2772 Yes 235155073 2.39 chr2:235158794-235158844 2.6954 chr2:235159510-235159560 2.7432 chr2:235159434-235159484 2.9200 Yes 235159497 2.40 chr2:235161714-235161764 2.0489 chr2:235161714-235161764 1.8302 Yes 235161739 2.41 chr2:235220624-235220674 1.4319 chr2:237210442-237310442 chr2:242612000-242712000 chr2:242661634-242661684 2.1945 chr2:242689805-242689855 1.8048 chr3:4946207-5046207 chr3:5016664-5016714 2.8256 chr3:5016664-5016714 1.9994 5016689 3.01 chr3:5036977-5037027 2.1626 chr3:5036977-5037027 2.1069 5037002 3.02 chr3:9759420-9859420 chr3:32358166-32458166 chr3:41166015-41266015 chr3:42469120-42569120 chr3:42561515-42561565 3.1457 chr3:42561356-42561406 2.4980 42561461 3.03 chr3:44678000-44778000 chr3:45192758-45292758 chr3:45216260-45216310 1.3204 chr3:47442449-47542449 chr3:47459486-47459536 1.9366 chr3:47459433-47459483 1.4751 47459485 3.04 chr3:47460186-47460236 2.3191 chr3:47460133-47460183 2.1686 47460185 3.05 chr3:47524247-47524297 3.1677 chr3:49134071-49234071 chr3:49147226-49147276 2.0769 chr3:49148300-49148350 2.5633 chr3:49183453-49183503 3.2574 chr3:49183453-49183503 2.0166 49183478 3.06 chr3:50308160-50408160 chr3:50328824-50328874 1.8339 chr3:50328877-50328927 2.1429 50328876 3.07 chr3:50407452-50407502 3.6057 chr3:50407452-50407502 3.0843 50407477 3.08 chr3:52404083-52504083 chr3:52415744-52415794 0.8934 chr3:52420179-52420229 3.7509 chr3:52420232-52420282 3.5086 Yes 52420231 3.09 chr3:52447174-52447224 1.8088 chr3:52449747-52449797 3.3990 Yes 52449772 3.10 chr3:56623399-56723399 chr3:65949549-66049549 chr3:99884261-99984261 chr3:100053223-100153223 chr3:100115765-100115815 1.4723 chr3:100124507-100124557 3.1952 chr3:100124507-100124557 3.2246 100124532 3.11 chr3:112826212-112926212 chr3:114898597-114998597 chr3:126746624-126846624 chr3:126815053-126815103 1.8313 chr3:126824001-126824051 4.9626 chr3:126824001-126824051 3.9259 Yes 126824026 3.12 chr3:129644726-129744726 chr3:130849007-131122007 chr3:130853082-130853132 4.3288 chr3:130853029-130853079 3.4482 130853081 3.13 chr3:130866051-130866101 2.5868 chr3:135133426-135281426 chr3:135135516-135135566 1.8184 chr3:135145503-135145553 3.3240 chr3:135145503-135145553 3.2680 135145528 3.14 chr3:135146826-135146876 2.7603 chr3:135146826-135146876 3.1606 135146851 3.15 chr3:135165492-135165542 2.8712 chr3:135165492-135165542 3.1724 Yes 135165517 3.16 chr3:135237833-135237883 3.9787 chr3:135237833-135237883 3.0101 135237858 3.17 chr3:135526104-135626104 chr3:135550329-135550379 1.5228 chr3:135553992-135554042 2.4170 chr3:150528266-150628266 chr3:150808480-150908480 chr3:150859259-150859309 1.9449 chr3:150859630-150859680 2.5356 150859470 3.18 chr3:150878801-150878851 2.2459 chr3:150878907-150878957 2.3083 150878879 3.19 chr3:156230160-156385160 chr3:156281413-156281463 2.5231 chr3:156283386-156283436 1.6361 Yes 156283411 3.20 chr3:156342916-156342966 1.9907

6 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr3:156350253-156350303 3.4764 chr3:156350253-156350303 3.5206 156350278 3.21 chr3:157705637-157925637 chr3:157733237-157733287 2.2518 Yes 157733262 3.22 chr3:157749511-157749561 3.3730 Yes 157749536 3.23 chr3:157803285-157803335 4.5060 chr3:157803053-157803103 4.1750 Yes 157803194 3.24 chr3:157804069-157804119 4.4406 chr3:157804069-157804119 4.1854 Yes 157804094 3.25 chr3:157804872-157804922 4.1037 chr3:157804872-157804922 3.4057 Yes 157804897 3.26 chr3:157816483-157816533 3.7350 chr3:157816483-157816533 4.2781 Yes 157816508 3.27 chr3:157819007-157819057 2.6250 Yes 157819032 3.28 chr3:157869004-157869054 3.1265 chr3:157869004-157869054 3.0313 Yes 157869029 3.29 chr3:157874746-157874796 4.6706 chr3:157874693-157874743 3.6093 Yes 157874745 3.30 chr3:157876727-157876777 1.6564 chr3:157876621-157876671 2.6493 Yes 157876699 3.31 chr3:161717000-161817000 chr3:184403746-184503746 chr3:184464804-184464854 2.1875 chr3:184464963-184465013 3.0061 184464909 3.32 chr3:184488200-184488250 2.4561 chr3:184497507-184497557 2.7061 chr3:189363422-189463422 chr3:189366261-189366311 1.9316 chr3:189386581-189386631 2.2981 chr3:189421792-189421842 4.1162 chr3:189421508-189421558 4.2559 189421675 3.33 chr3:189427019-189427069 3.2910 chr3:189427019-189427069 2.5186 189427044 3.34 chr3:189427072-189427122 2.4401 chr3:189428209-189428259 2.2032 chr3:189431773-189431823 1.9972 chr3:189441689-189441739 2.6650 chr3:190781917-190881917 chr3:191472917-191572917 chr4:64401-164401 chr4:6754000-7004000 chr4:6799955-6800005 2.2483 chr4:6799955-6800005 2.0610 Yes 6799980 4.01 chr4:6813228-6813278 4.5138 chr4:6813281-6813331 3.4816 6813280 4.02 chr4:6870798-6870848 4.3328 chr4:6870798-6870848 3.6339 6870823 4.03 chr4:6873328-6873378 2.3750 chr4:6883505-6883555 3.0667 chr4:6883505-6883555 2.6280 6883530 4.04 chr4:6900960-6901010 2.5021 chr4:6900960-6901010 2.1539 Yes 6900985 4.05 chr4:14631790-14731790 chr4:15309000-15409000 chr4:15566240-15666240 chr4:15572923-15572973 2.2010 chr4:15572817-15572867 2.6091 15572895 4.06 chr4:17410000-17510000 chr4:49072000-49172000 chr4:54215295-54315295 chr4:54218335-54218385 3.5863 chr4:54218226-54218276 2.5933 54218306 4.07 chr4:54225212-54225262 3.2152 chr4:54225212-54225262 1.6394 Yes 54225237 4.08 chr4:54236530-54236580 2.9997 Yes 54236555 4.09 chr4:54238828-54238878 2.7308 chr4:54243620-54243670 2.2637 chr4:54243620-54243670 2.5022 Yes 54243645 4.10 chr4:54244815-54244865 2.6163 chr4:54244815-54244865 2.3502 54244840 4.11 chr4:54265710-54265760 2.5459 chr4:54265951-54266001 2.4569 54265856 4.12 chr4:68994573-69094573 chr4:69070701-69070751 3.0954 chr4:74921000-75721000 chr4:74971299-74971349 2.5552 chr4:74971299-74971349 3.6363 Yes 74971324 4.13 chr4:75099607-75099657 2.6346 Yes 75099632 4.14 chr4:75126425-75126475 1.8928 chr4:75126425-75126475 2.3605 Yes 75126450 4.15 chr4:75330652-75330702 2.0645 Yes 75330677 4.16 chr4:75331140-75331190 2.7193 chr4:75340013-75340063 1.5526 chr4:75450091-75450141 2.1427 chr4:75450091-75450141 2.3597 Yes 75450116 4.17 chr4:75461990-75462040 2.6256 chr4:75539055-75539105 2.0262 chr4:75539055-75539105 2.4518 Yes 75539080 4.18 chr4:75641308-75641358 1.8253 chr4:75654070-75654120 1.9774 chr4:75704120-75704170 2.0062 chr4:75704014-75704064 2.3268 Yes 75704092 4.19 chr4:81301432-81401432 chr4:84343068-84443068 chr4:87823063-87923063 chr4:88077447-88177447 chr4:88119582-88119632 2.2209 chr4:88169889-88169939 3.8809 chr4:88169699-88169749 3.5124 88169819 4.20 chr4:89820824-89920824 chr4:100792003-100892003 chr4:103989341-104089341 chr4:109397182-109497182 chr4:124055467-124155467 chr4:124625560-124725560 chr4:129189165-129490165 chr4:154008739-154271739 chr4:154216894-154216944 1.0659 chr4:154217077-154217127 1.9160 154217011 4.21 chr4:154251801-154251851 2.7013 chr4:154251589-154251639 2.2163 154251720 4.22 chr4:154260286-154260336 2.4368 chr4:154260286-154260336 2.5064 154260311 4.23 chr4:154262838-154262888 1.8290 chr4:154262732-154262782 1.8165 154262810 4.24 chr4:154268225-154268275 3.0293 chr4:154268225-154268275 3.0377 154268250 4.25 chr4:154270667-154270717 1.4961 chr4:154270826-154270876 1.5929 154270772 4.26 chr4:154913045-155013045 chr4:154931213-154931263 3.3211 chr4:154930909-154930959 3.3901 154931086 4.27 chr4:171336102-171436102 chr4:175768341-175868341 chr4:175835013-175835063 1.6217 chr4:175835866-175835916 1.9854 chr4:186050364-186172364 chr4:186051809-186051859 2.7012 chr4:186054257-186054307 2.3512 chr4:186089723-186089773 2.4757 chr4:186089723-186089773 2.8403 186089748 4.28 chr4:186109889-186109939 4.1905 chr4:186109889-186109939 3.8956 Yes 186109914 4.29 chr4:186170408-186170458 2.6751 chr4:187437822-187537822 chr5:1115109-1215109 chr5:1214527-1214577 2.4548 chr5:1214686-1214736 2.2771 Yes 1214632 5.01 chr5:6440000-6540000 chr5:9549158-9649158 chr5:9599702-9599752 1.4324

7 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr5:14146828-14246828 chr5:14185182-14185232 2.9211 chr5:14185182-14185232 2.4500 14185207 5.02 chr5:14214526-14214576 3.0793 chr5:14584931-14684931 chr5:14585691-14585741 2.5703 chr5:14587918-14587968 1.9727 chr5:14606949-14606999 3.3819 chr5:14606790-14606840 2.5985 14606895 5.03 chr5:14679337-14679387 2.8394 chr5:14874876-14974876 chr5:14896010-14896060 2.4332 chr5:14896116-14896166 2.6369 14896088 5.04 chr5:38581253-38681253 chr5:52762351-52862351 chr5:54816630-54916630 chr5:54883243-54883293 1.2515 chr5:57741844-57841844 chr5:59769515-59869515 chr5:59787305-59787355 2.5992 chr5:59787305-59787355 1.8942 59787330 5.05 chr5:64763460-64863460 chr5:65003840-65103840 chr5:73922273-74022273 chr5:73974748-73974798 1.4687 chr5:73990996-73991046 1.2692 chr5:73999063-73999113 1.5565 chr5:74018042-74018092 2.1992 chr5:77791867-77891867 chr5:77847698-77847748 5.2092 chr5:77847607-77847657 3.7538 77847678 5.06 chr5:77850199-77850249 2.3472 chr5:90664877-90764877 chr5:95273531-95373531 chr5:95322530-95322580 1.9462 chr5:95322159-95322209 1.2501 95322370 5.07 chr5:95368574-95368624 3.8188 chr5:95368574-95368624 3.4276 95368599 5.08 chr5:115155398-115255398 chr5:115158028-115158078 3.8836 chr5:115157975-115158025 3.5305 115158027 5.09 chr5:115158449-115158499 3.6796 chr5:115158502-115158552 3.6042 115158501 5.10 chr5:115206265-115206315 3.8193 chr5:115206265-115206315 3.9021 115206290 5.11 chr5:118669628-118769628 chr5:118698482-118698532 3.1456 chr5:118698535-118698585 2.7956 118698534 5.12 chr5:118723394-118723444 1.0877 chr5:118724997-118725047 1.7644 chr5:118724939-118724989 2.4674 118724993 5.13 chr5:118762648-118762698 2.5316 chr5:121165548-121265548 chr5:1214323-1214373 2.0981 chr5:122350324-122450324 chr5:133839696-133939696 chr5:133873007-133873057 2.4250 Yes 133873032 5.14 chr5:133875480-133875530 2.9209 chr5:133875480-133875530 2.8484 Yes 133875505 5.15 chr5:139656358-139756358 chr5:142080475-142180475 chr5:142080747-142080797 2.0361 chr5:142080747-142080797 2.2861 Yes 142080772 5.16 chr5:14209828-14209878 1.8718 chr5:142103489-142103539 3.6371 chr5:142103489-142103539 2.1573 142103514 5.17 chr5:142113295-142113345 3.1375 chr5:142113242-142113292 3.1743 142113294 5.18 chr5:142131250-142131300 2.9142 chr5:142131197-142131247 1.6849 142131249 5.19 chr5:142132731-142132781 1.4506 chr5:142144953-142145003 2.5140 chr5:142745270-142845270 chr5:142790988-142791038 2.3580 chr5:147578000-147678000 chr5:147628457-147628507 4.0095 chr5:147628457-147628507 3.4429 147628482 5.20 chr5:147674286-147674336 1.7291 chr5:148667801-148767801 chr5:148683192-148683242 1.6758 chr5:148683078-148683128 2.3066 148683160 5.21 chr5:148711039-148711089 2.4438 chr5:148711039-148711089 1.8021 148711064 5.22 chr5:14915539-14915589 1.9992 chr5:148719237-148719287 3.0259 chr5:148719343-148719393 1.9589 148719315 5.23 chr5:148720553-148720603 4.1200 chr5:148720500-148720550 3.1846 148720552 5.24 chr5:149270638-149370638 chr5:149298707-149298757 1.2403 chr5:149299078-149299128 1.8557 chr5:149299078-149299128 2.3794 149299103 5.25 chr5:149304671-149304721 1.4558 chr5:149304671-149304721 2.8785 149304696 5.26 chr5:149358826-149358876 3.0713 chr5:150088059-150188059 chr5:150140132-150140182 2.6787 chr5:150140629-150140679 3.4559 chr5:150141745-150141795 2.8174 chr5:170729271-170829271 chr5:170778874-170778924 1.9794 chr5:170778874-170778924 1.7838 170778899 5.27 chr5:170795770-170795820 1.6111 chr5:170798278-170798328 1.5874 chr5:170799025-170799075 2.2377 chr5:170798919-170798969 1.6724 170798997 5.28 chr5:170808872-170808922 2.6457 chr5:170808660-170808710 2.3976 170808791 5.29 chr5:171012000-171112000 chr5:171042630-171042680 2.1466 chr5:173198794-173298794 chr5:173244118-173244168 2.2540 chr5:173244065-173244115 2.7070 173244117 5.30 chr5:173244509-173244559 1.2197 chr5:174034207-174134207 chr5:175107886-175377886 chr5:175227960-175228010 1.5716 chr5:175227960-175228010 2.8403 175227985 5.31 chr5:175311219-175311269 3.6342 chr5:175311272-175311322 3.3646 175311271 5.32 chr5:179217462-179317462 chr5:179217963-179218013 1.2898 chr5:179266306-179266356 3.6494 chr5:179266306-179266356 3.4564 Yes 179266331 5.33 chr5:179266853-179266903 1.8818 chr5:179266800-179266850 2.4224 179266852 5.34 chr6:1505679-1605679 chr6:1518525-1518575 1.3264 chr6:1522970-1523020 3.8295 chr6:1522970-1523020 2.5706 1522995 6.01 chr6:1524438-1524488 4.7855 chr6:1524491-1524541 3.4225 1524490 6.02 chr6:1556299-1556349 1.5322 chr6:1582753-1582803 4.1161 chr6:1582753-1582803 2.5409 1582778 6.03 chr6:1586754-1586804 1.9595 chr6:1586860-1586910 1.8317 1586832 6.04 chr6:2050845-2240845 chr6:2798506-2898506 chr6:7485430-7585430 chr6:7503480-7503530 3.0309 chr6:7503480-7503530 2.3192 7503505 6.05 chr6:7506909-7506959 1.8942 chr6:7507078-7507128 2.6989 7507019 6.06 chr6:7563758-7563808 1.9672 chr6:14175743-14275743 chr6:16296789-16396789 chr6:19895595-19995595 chr6:19975586-19975636 1.6580 chr6:21651950-21751950 chr6:21665326-21665376 2.1764 chr6:26216327-26316327 chr6:31196432-31296432 chr6:31201477-31201527 4.2042 chr6:31201424-31201474 3.8911 31201476 6.07

8 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr6:33348682-33448682 chr6:33354477-33354527 1.7248 chr6:33364617-33364667 2.5628 chr6:33364617-33364667 1.8090 33364642 6.08 chr6:33772660-33872660 chr6:33806527-33806577 3.0603 chr6:33806527-33806577 2.4402 33806552 6.09 chr6:33822092-33822142 0.9728 chr6:33848238-33848288 1.7566 chr6:33848238-33848288 1.9117 33848263 6.10 chr6:33862286-33862336 1.2712 chr6:33862286-33862336 1.4448 33862311 6.11 chr6:35368363-35468363 chr6:35374086-35374136 1.0260 chr6:35374086-35374136 1.3488 35374111 6.12 chr6:35648692-35814692 chr6:35666402-35666452 3.3836 chr6:35666349-35666399 3.4128 35666401 6.13 chr6:35672816-35672866 2.1560 chr6:35677742-35677792 2.8206 chr6:35677910-35677960 3.0781 35677851 6.14 chr6:35686750-35686800 3.9809 chr6:35686697-35686747 3.3200 35686749 6.15 chr6:35767464-35767514 1.8124 chr6:35767464-35767514 1.8052 35767489 6.16 chr6:35801653-35801703 3.2291 chr6:35801653-35801703 3.2324 35801678 6.17 chr6:35802980-35803030 3.3346 chr6:35803086-35803136 3.9910 35803058 6.18 chr6:35803961-35804011 2.2221 chr6:35803961-35804011 2.0513 35803986 6.19 chr6:35805517-35805567 3.4880 chr6:35805611-35805661 2.1441 35805589 6.20 chr6:37379768-37479768 chr6:37381938-37381988 2.6926 chr6:37381938-37381988 2.1134 37381963 6.21 chr6:37416245-37416295 2.1950 chr6:37446022-37446072 3.2339 chr6:37446022-37446072 3.1553 37446047 6.22 chr6:43542768-43642768 chr6:43567968-43568018 1.7917 chr6:43567915-43567965 1.7396 43567967 6.23 chr6:43568392-43568442 2.1445 chr6:43569678-43569728 2.7079 chr6:43569890-43569940 2.6375 43569809 6.24 chr6:43571331-43571381 2.2227 chr6:43571331-43571381 2.4732 43571356 6.25 chr6:43571967-43572017 2.8465 chr6:43572391-43572441 1.2200 chr6:43795923-43895923 chr6:43822018-43822068 2.0175 chr6:43822018-43822068 1.7841 43822043 6.26 chr6:47711558-47811558 chr6:47773903-47773953 3.4292 chr6:47773903-47773953 3.7742 47773928 6.27 chr6:52010382-52110382 chr6:52032904-52032954 2.2650 chr6:52032904-52032954 2.0426 52032929 6.28 chr6:52038606-52038656 1.9284 chr6:56581422-56866422 chr6:56636841-56636891 1.7092 chr6:56636841-56636891 1.8207 Yes 56636866 6.29 chr6:56798496-56798546 2.9817 chr6:56815487-56815537 2.2573 chr6:56815540-56815590 2.3801 Yes 56815539 6.30 chr6:56844207-56844257 2.4342 chr6:56844207-56844257 1.5976 Yes 56844232 6.31 chr6:64289878-64389878 chr6:86166527-86266527 chr6:86184701-86184751 1.4436 chr6:101372632-101472632 chr6:107016422-107116422 chr6:107068705-107068755 1.5729 chr6:107075283-107075333 3.7072 chr6:107075283-107075333 2.4723 107075308 6.32 chr6:117643413-117743413 chr6:130023063-130123063 chr6:130047064-130047114 1.8277 chr6:130111263-130111313 2.2147 chr6:134487695-134587695 chr6:134525907-134525957 1.6768 chr6:134525687-134525737 1.6189 Yes 134525822 6.33 chr6:134536116-134536166 2.1779 chr6:134536116-134536166 2.5067 Yes 134536141 6.34 chr6:134538864-134538914 3.6094 chr6:134538864-134538914 3.7947 Yes 134538889 6.35 chr6:138180273-138280273 chr6:138212760-138212810 1.8424 chr6:138236227-138236277 2.6271 chr6:138236227-138236277 3.0604 138236252 6.36 chr6:138238511-138238561 2.0170 chr6:138245542-138245592 1.7659 chr6:138255295-138255345 2.3576 chr6:14201424-14201474 2.5608 chr6:149060156-149160156 chr6:149109209-149109259 2.4278 chr6:149109368-149109418 2.7234 149109314 6.37 chr6:149110886-149110936 2.7268 chr6:150506346-150606346 chr6:150589599-150589649 2.7242 chr6:150589599-150589649 2.0784 150589624 6.38 chr6:152730593-152830593 chr6:153000648-153100648 chr6:158654100-158754100 chr6:158702916-158702966 2.6274 chr6:158703066-158703116 2.8489 158703016 6.39 chr6:158714692-158714742 2.4757 chr6:158714354-158714404 2.6131 158714548 6.40 chr6:158715591-158715641 2.6280 chr6:160689693-161145693 chr6:160690438-160690488 2.9726 chr6:160690438-160690488 2.0347 160690463 6.41 chr6:160726569-160726619 4.1727 chr6:160729471-160729521 3.7551 chr6:160729683-160729733 2.9562 160729602 6.42 chr6:160730715-160730765 2.0318 chr6:160759463-160759513 2.4888 chr6:160759304-160759354 2.1877 160759409 6.43 chr6:160778238-160778288 3.5245 chr6:160778291-160778341 3.2190 160778290 6.44 chr6:160806777-160806827 2.9015 chr6:160806777-160806827 2.8726 160806802 6.45 chr6:160869495-160869545 2.3037 chr6:163069211-163169211 chr6:16386123-16386173 2.2368 chr6:167290488-167390488 chr7:408000-508000 chr7:13752004-13852004 chr7:14745000-14845000 chr7:20093985-20193985 chr7:20142926-20142976 1.8970 chr7:20143403-20143453 2.7643 chr7:20143403-20143453 1.9599 20143428 7.01 chr7:20145147-20145197 2.2178 chr7:20145147-20145197 2.2187 20145172 7.02 chr7:20153876-20153926 3.1379 chr7:20153770-20153820 3.2400 20153848 7.03 chr7:20175440-20175490 2.5239 chr7:20175440-20175490 3.2728 20175465 7.04 chr7:21306072-21406072 chr7:22490059-22590059 chr7:22531125-22531175 1.9992 chr7:22531125-22531175 2.2528 22531150 7.05 chr7:23009555-23109555 chr7:23082943-23082993 1.5824 chr7:23086000-23086050 1.7673 chr7:23106752-23106802 1.4423 chr7:23294839-23394839 chr7:38081000-38181000 chr7:41465946-41565946 chr7:41509139-41509189 1.8977 chr7:41509139-41509189 2.1588 41509164 7.06 chr7:45650700-45784700 chr7:45693454-45693504 4.4158 chr7:45693401-45693451 1.8791 45693453 7.07 chr7:45702499-45702549 4.9147 chr7:45702446-45702496 3.2084 45702498 7.08 chr7:75851214-75951214 chr7:76920410-77020410

9 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr7:79358790-79458790 chr7:79425072-79425122 1.9544 chr7:92372331-92472331 chr7:93114716-93214716 chr7:93125297-93125347 3.2631 chr7:93125543-93125593 3.0288 93125445 7.09 chr7:107187755-107287755 chr7:107206478-107206528 4.2503 chr7:107206425-107206475 3.9003 107206477 7.10 chr7:107206807-107206857 3.9608 chr7:107207394-107207444 3.1455 chr7:107213545-107213595 1.7869 chr7:129476944-129576944 chr7:137018500-137263500 chr7:137096084-137096134 2.3027 chr7:137096137-137096187 4.1432 137096136 7.11 chr7:137099891-137099941 1.8381 chr7:137127604-137127654 1.3959 chr7:137134984-137135034 2.8395 chr7:137135143-137135193 2.7419 137135089 7.12 chr7:137142264-137142314 2.4028 chr7:137142041-137142091 2.2126 137142178 7.13 chr7:137142704-137142754 2.8128 chr7:137143530-137143580 1.5497 chr7:137233082-137233132 3.2311 chr7:137233082-137233132 2.9303 137233107 7.14 chr7:137240940-137240990 1.5780 chr7:137241258-137241308 2.5943 137241124 7.15 chr7:141098862-141198862 chr7:141154658-141154708 2.4336 chr7:141154605-141154655 2.9643 141154657 7.16 chr7:141161355-141161405 3.6966 chr7:141161454-141161504 2.7256 141161430 7.17 chr7:147783580-147883580 chr8:18061894-18161894 chr8:18080802-18080852 1.8013 chr8:18110957-18111007 2.1798 chr8:23546395-23646395 chr8:28565071-28665071 chr8:28621540-28621590 2.0997 chr8:28621739-28621789 2.7797 28621665 8.01 chr8:29214104-29314104 chr8:29254910-29254960 2.0031 chr8:37826161-37926161 chr8:37840750-37840800 3.2721 chr8:37840750-37840800 2.8979 37840775 8.02 chr8:37880406-37880456 2.0523 chr8:37880618-37880668 1.9324 37880537 8.03 chr8:41236137-41336137 chr8:42134351-42234351 chr8:49946541-50046541 chr8:49963430-49963480 3.0598 chr8:49963430-49963480 2.7106 Yes 49963455 8.04 chr8:82041858-82236858 chr8:82067302-82067352 2.2700 chr8:82074204-82074254 3.1267 chr8:82073992-82074042 2.1754 82074123 8.05 chr8:82104782-82104832 3.3743 chr8:82104782-82104832 2.4144 82104807 8.06 chr8:82110360-82110410 4.5902 chr8:82110413-82110463 3.5388 82110412 8.07 chr8:82122843-82122893 2.5081 chr8:82122896-82122946 2.3858 82122895 8.08 chr8:82160431-82160481 3.9400 chr8:82160263-82160313 3.6919 82160372 8.09 chr8:82188543-82188593 3.7097 chr8:82188649-82188699 2.0164 82188621 8.10 chr8:82225161-82225211 2.0165 chr8:82629000-82729000 chr8:82692979-82693029 2.0582 chr8:82692979-82693029 2.2729 82693004 8.11 chr8:86513497-86613497 chr8:86552431-86552481 1.8554 chr8:87540037-87640037 chr8:95293733-95393733 chr8:95314484-95314534 1.7577 chr8:99325797-99425797 chr8:99328651-99328701 2.6942 chr8:99328651-99328701 1.9077 99328676 8.12 chr8:99363565-99363615 3.4800 chr8:99363618-99363668 3.2533 99363617 8.13 chr8:99378873-99378923 3.6522 chr8:104172096-104272096 chr8:127589648-127689648 chr8:128767685-128867685 chr8:128816393-128816443 1.6740 chr8:128841461-128841511 2.6910 chr8:134328680-134428680 chr8:134350616-134350666 2.4171 chr8:134350563-134350613 2.0884 134350615 8.14 chr8:134403628-134403678 2.2723 chr8:134403701-134403751 1.7632 134403690 8.15 chr8:134407643-134407693 2.2216 chr8:134408349-134408399 3.6752 chr8:134603344-134703344 chr8:134652095-134652145 1.7307 chr8:145071531-145171531 chr9:5390558-5490558 chr9:33387590-33487590 chr9:33398091-33398141 1.6106 chr9:33398409-33398459 2.4776 chr9:33398409-33398459 2.0686 33398434 9.01 chr9:33415175-33415225 2.0950 chr9:33427116-33427166 1.8651 chr9:33427309-33427359 1.1433 33427238 9.02 chr9:33448503-33448553 1.8304 chr9:33448503-33448553 2.5475 33448528 9.03 chr9:33451598-33451648 2.0571 chr9:33451598-33451648 1.7181 Yes 33451623 9.04 chr9:35102058-35202058 chr9:71562962-71662962 chr9:71627757-71627807 2.5058 chr9:71627757-71627807 2.3218 71627782 9.05 chr9:72159446-72259446 chr9:72210415-72210465 4.3379 chr9:72210521-72210571 4.0028 72210493 9.06 chr9:72241297-72241347 2.1033 chr9:79366431-79466431 chr9:88785396-88885396 chr9:88846235-88846285 1.8569 chr9:88865745-88865795 2.0027 chr9:88865798-88865848 1.7649 88865797 9.07 chr9:92274343-92374343 chr9:92319054-92319104 1.4563 chr9:92342845-92342895 2.7555 chr9:92343384-92343434 2.9533 chr9:92343437-92343487 1.9449 92343436 9.08 chr9:92347041-92347091 1.8193 chr9:92346988-92347038 1.5301 92347040 9.09 chr9:96210224-96310224 chr9:101190717-101290717 chr9:101241662-101241712 3.6688 chr9:101241662-101241712 3.5246 101241687 9.10 chr9:107281310-107381310 chr9:107346552-107346602 1.3597 chr9:109013573-109212573 chr9:109087680-109087730 4.5526 chr9:109087733-109087783 3.8828 109087732 9.11 chr9:109093467-109093517 3.3377 chr9:109093467-109093517 3.1092 109093492 9.12 chr9:109093769-109093819 3.6277 chr9:109094434-109094484 4.8907 chr9:109094487-109094537 4.3064 109094486 9.13 chr9:109095795-109095845 2.2642 chr9:109128506-109128556 2.0860 chr9:109128665-109128715 2.9166 109128611 9.14 chr9:109141966-109142016 2.3314 chr9:109144646-109144696 2.1672 chr9:109144646-109144696 1.6856 109144671 9.15 chr9:109146184-109146234 2.5803 chr9:109146184-109146234 2.0206 109146209 9.16 chr9:109150151-109150201 3.9866 chr9:109150151-109150201 2.7014 109150176 9.17 chr9:109572143-109672143

10 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr9:110829920-110929920 chr9:110878328-110878378 2.6307 chr9:121162099-121262099 chr9:121214806-121214856 3.5662 chr9:121215128-121215178 3.2291 121214992 9.18 chr9:124592706-124692706 chr9:128674000-128774000 chr9:128721266-128721316 2.2066 chr9:128749365-128749415 2.7162 chr9:128749312-128749362 1.1965 128749364 9.19 chr9:128749842-128749892 2.5699 chr9:128753244-128753294 2.4176 chr9:128753191-128753241 1.3369 128753243 9.20 chr9:128754292-128754342 2.4991 chr9:128754292-128754342 1.8286 128754317 9.21 chr9:128762505-128762555 2.2174 chr9:128762505-128762555 2.1715 128762530 9.22 chr9:128970080-129070080 chr9:128985105-128985155 1.5706 chr9:131357000-131482000 chr9:131362160-131362210 2.1916 chr9:131434616-131434666 0.9959 chr9:131435411-131435461 2.6974 chr10:5428582-5528582 chr10:5436705-5436755 2.2494 chr10:5436705-5436755 2.3125 5436730 10.01 chr10:5478365-5478415 2.1791 chr10:5478311-5478361 2.2807 5478363 10.02 chr10:5482076-5482126 2.2000 chr10:5482076-5482126 1.8598 5482101 10.03 chr10:5520289-5520339 1.7678 chr10:5520342-5520392 2.1062 Yes 5520341 10.04 chr10:5698547-5798547 chr10:5714371-5714421 4.2994 chr10:5714265-5714315 3.7865 Yes 5714343 10.05 chr10:5721167-5721217 3.3590 chr10:5721167-5721217 2.2022 Yes 5721192 10.06 chr10:5736448-5736498 2.4987 chr10:5742145-5742195 1.9789 chr10:7343000-7543000 chr10:7343259-7343309 1.8083 chr10:7392157-7392207 3.0040 chr10:7490966-7491016 1.7033 chr10:7541755-7541805 3.9038 chr10:7541821-7541871 2.3892 7541813 10.07 chr10:16468972-16568972 chr10:18938318-19038318 chr10:18944639-18944689 2.2150 chr10:27519718-27619718 chr10:47167012-47267012 chr10:47227125-47227175 2.3154 chr10:47237100-47237150 2.4685 chr10:47238364-47238414 2.3306 chr10:47238311-47238361 2.1167 47238363 10.08 chr10:47246909-47246959 2.2842 chr10:47246909-47246959 1.9983 47246934 10.09 chr10:52003743-52103743 chr10:52016396-52016446 2.2157 chr10:52016396-52016446 2.7284 52016421 10.10 chr10:52059847-52059897 1.5908 chr10:52059794-52059844 2.3461 52059846 10.11 chr10:53694046-53794046 chr10:54151466-54251466 chr10:54174401-54174451 1.8238 chr10:61559494-61869494 chr10:61605308-61605358 2.0215 chr10:61605362-61605412 2.2386 61605360 10.12 chr10:61635604-61635654 2.8035 chr10:61635657-61635707 1.6817 61635656 10.13 chr10:63278000-63523000 chr10:63448557-63448607 1.2561 chr10:63448557-63448607 1.8905 63448582 10.14 chr10:63478105-63478155 3.1841 chr10:63478105-63478155 3.1705 63478130 10.15 chr10:63478744-63478794 2.0640 chr10:63478744-63478794 1.7597 63478769 10.16 chr10:63482142-63482192 2.8438 chr10:63482142-63482192 3.1896 63482167 10.17 chr10:63493581-63493631 2.4901 chr10:63493740-63493790 2.7804 63493686 10.18 chr10:63499498-63499548 3.2285 chr10:63499387-63499437 3.2539 63499468 10.19 chr10:64196133-64296133 chr10:64648988-64748988 chr10:70467833-70567833 chr10:70491310-70491360 2.0724 chr10:70600064-70700064 chr10:70652612-70652662 2.3741 chr10:70652864-70652914 2.6879 70652763 10.20 chr10:70663050-70663100 1.9375 chr10:73653682-73753682 chr10:73673814-73673864 3.3903 chr10:73678081-73678131 2.9615 chr10:73678709-73678759 3.2340 chr10:73678497-73678547 3.0434 73678628 10.21 chr10:73678921-73678971 2.7052 chr10:73685206-73685256 3.2076 chr10:73685206-73685256 3.2248 73685231 10.22 chr10:73686137-73686187 3.5731 chr10:73686137-73686187 2.5619 73686162 10.23 chr10:73702614-73702664 1.4760 chr10:73727090-73727140 2.6071 chr10:73728163-73728213 1.6098 chr10:73728269-73728319 1.5589 73728241 10.24 chr10:73739217-73739267 2.2125 chr10:73739111-73739161 2.3608 73739189 10.25 chr10:75290895-75390895 chr10:75322458-75322508 1.7983 chr10:75322759-75322809 2.2861 75322634 10.26 chr10:80475000-80720000 chr10:80501992-80502042 2.6169 chr10:80501992-80502042 1.5748 80502017 10.27 chr10:80517405-80517455 1.6965 chr10:80676193-80676243 1.4912 chr10:92621012-92721012 chr10:92671145-92671195 2.5257 chr10:92671089-92671139 2.9502 92671142 10.28 chr10:92719878-92719928 2.3569 chr10:95196398-95296398 chr10:95212818-95212868 2.5727 chr10:95212818-95212868 2.7302 95212843 10.29 chr10:95225272-95225322 2.5731 chr10:95225219-95225269 2.6257 95225271 10.30 chr10:101641871-101791871 chr10:101676997-101677047 2.7374 chr10:101681227-101681277 2.1441 chr10:101682576-101682626 2.6433 chr10:101682522-101682572 2.4578 101682574 10.31 chr10:101713274-101713324 2.4250 chr10:101713274-101713324 2.3829 101713299 10.32 chr10:101716009-101716059 2.2139 chr10:101715916-101715966 2.5929 101715988 10.33 chr10:102046761-102146761 chr10:102112270-102112320 1.7398 chr10:102120957-102121007 1.4772 chr10:103543667-103643667 chr10:106033653-106133653 chr10:106069047-106069097 2.1706 chr10:106069153-106069203 3.1918 106069125 10.34 chr10:106080214-106080264 1.9831 chr10:106081454-106081504 3.1181 chr10:106081454-106081504 3.4089 106081479 10.35 chr10:106090212-106090262 2.5819 chr10:106090159-106090209 1.4339 106090211 10.36 chr10:112197614-112297614 chr10:112206690-112206740 1.4121 chr10:112251199-112251249 2.1965 chr10:115554409-115654409 chr10:115593883-115593933 4.7095 chr10:115593883-115593933 4.0003 115593908 10.37 chr10:118320807-118420807 chr10:121350871-121450871 chr10:121393021-121393071 2.5024 chr10:121402870-121402920 2.3370 chr10:121405331-121405381 4.2907 chr10:121405172-121405222 3.2211 121405277 10.38 chr10:121408183-121408233 1.9671 chr10:121408077-121408127 1.9909 121408155 10.39

11 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr10:121416082-121416132 2.6036 chr10:121417098-121417148 2.9444 chr10:121417098-121417148 2.4383 121417123 10.40 chr10:121430379-121430429 1.3542 chr10:131602081-131702081 chr11:635740-735740 chr11:638601-638651 4.1883 chr11:638601-638651 3.1550 638626 11.01 chr11:654755-654805 3.5363 chr11:655391-655441 3.3931 chr11:655126-655176 2.9532 655284 11.02 chr11:662435-662485 3.4018 chr11:679755-679805 4.0631 chr11:679702-679752 3.4395 679754 11.03 chr11:1767478-1867478 chr11:1798956-1799006 1.6277 chr11:1805274-1805324 2.5510 chr11:1805274-1805324 1.9190 1805299 11.04 chr11:1807076-1807126 2.0494 chr11:1807129-1807179 2.0359 1807128 11.05 chr11:2813537-2913537 chr11:2855524-2855574 1.7703 chr11:2855524-2855574 1.7936 2855549 11.06 chr11:2889782-2889832 1.7491 chr11:2891054-2891104 1.7476 chr11:8671074-8939074 chr11:8695743-8695793 2.3379 chr11:8739977-8740027 2.4353 chr11:8745956-8746006 1.7919 chr11:8745834-8745884 2.7970 8745920 11.07 chr11:8752354-8752404 2.1414 chr11:8753448-8753498 2.3755 chr11:8787458-8787508 4.0558 chr11:8787564-8787614 2.8993 8787536 11.08 chr11:8812223-8812273 2.0339 chr11:15948494-16504494 chr11:16075850-16075900 1.8781 chr11:16764535-17042535 chr11:16770185-16770235 1.4863 chr11:16960697-16960747 0.9456 chr11:16991009-16991059 3.2621 chr11:16991009-16991059 3.0027 16991034 11.09 chr11:29945064-30045064 chr11:32758064-32858064 chr11:32854093-32954093 chr11:45733911-45833911 chr11:57142049-57242049 chr11:57164063-57164113 1.9968 chr11:58646000-58746000 chr11:63155497-63284497 chr11:63448654-63548654 chr11:64828865-64928865 chr11:64835521-64835571 2.2239 chr11:64835521-64835571 2.4136 64835546 11.10 chr11:64876344-64876394 2.4423 chr11:64876344-64876394 2.0667 64876369 11.11 chr11:64879852-64879902 2.7973 chr11:64882284-64882334 4.3584 chr11:64882390-64882440 3.7104 64882362 11.12 chr11:65374573-65474573 chr11:66497466-66597466 chr11:69115053-69215053 chr11:69169880-69169930 2.3114 chr11:69169880-69169930 1.4713 69169905 11.13 chr11:73718150-73837150 chr11:73783145-73783195 3.0483 chr11:73783145-73783195 2.1958 73783170 11.14 chr11:74690521-74790521 chr11:74761268-74761318 4.2396 chr11:86139210-86239210 chr11:100413465-100556465 chr11:101643403-101743403 chr11:101682406-101682456 3.1721 chr11:101693279-101693329 2.4870 chr11:101693279-101693329 3.1097 101693304 11.15 chr11:101707942-101707992 3.2736 chr11:101707995-101708045 2.0500 101707994 11.16 chr11:101856688-101956688 chr11:101936546-101936596 2.6506 chr11:101939658-101939708 1.9664 chr11:101939658-101939708 1.9897 101939683 11.17 chr11:114830325-114930325 chr11:128192478-128292478 chr11:128292327-128292377 3.5888 chr11:128292327-128292377 2.8829 128292352 11.18 chr12:3006817-3106817 chr12:3098948-3098998 1.2751 chr12:4973345-5073345 chr12:6304976-6404976 chr12:6318512-6318562 1.2958 chr12:6318512-6318562 1.1716 6318537 12.01 chr12:6321574-6321624 1.8966 chr12:6352583-6352633 2.7253 chr12:6352583-6352633 2.4536 6352608 12.02 chr12:6355969-6356019 2.1703 chr12:6356022-6356072 2.1828 6356021 12.03 chr12:6364459-6364509 2.5007 chr12:6364459-6364509 1.4413 6364484 12.04 chr12:12711575-12811575 chr12:12747711-12747761 1.9359 chr12:12885222-12985222 chr12:12899534-12899584 2.8500 chr12:12916681-12916731 2.4682 chr12:12927715-12927765 1.5183 chr12:27966183-28066183 chr12:28063359-28063409 4.2423 chr12:28063359-28063409 2.5491 28063384 12.05 chr12:29738959-29878959 chr12:29779208-29779258 1.4557 chr12:29780174-29780224 3.9254 chr12:29780280-29780330 2.3017 29780252 12.06 chr12:31953619-32053619 chr12:32496360-32596360 chr12:32498395-32498445 2.1480 chr12:32498508-32498558 2.6824 32498477 12.07 chr12:32578363-32578413 3.0676 chr12:32578363-32578413 4.0902 32578388 12.08 chr12:32593110-32593160 1.4170 chr12:45709915-45809915 chr12:45713163-45713213 1.9752 chr12:45713163-45713213 2.7048 Yes 45713188 12.09 chr12:48797366-49014366 chr12:49394127-49494127 chr12:51103824-51203824 chr12:51132328-51132378 1.6500 chr12:51173444-51173494 2.2406 chr12:51174931-51174981 4.3300 chr12:51174931-51174981 3.5625 51174956 12.10 chr12:51188463-51188513 2.7526 chr12:51196203-51196253 2.7643 chr12:51196256-51196306 2.8044 51196255 12.11 chr12:51198845-51198895 0.9943 chr12:51200724-51200774 2.2901 chr12:51201313-51201363 2.1888 chr12:51201313-51201363 2.0897 51201338 12.12 chr12:51202267-51202317 2.6309 chr12:51202214-51202264 3.3662 51202266 12.13 chr12:51248610-51348610 chr12:51311445-51311495 2.0713 chr12:51336109-51336159 2.8577 chr12:51343485-51343535 2.5875 chr12:51733581-51833581 chr12:51746332-51746382 2.6554 chr12:51746279-51746329 2.1140 51746331 12.14 chr12:51759879-51759929 2.6735 chr12:51759879-51759929 2.9555 51759904 12.15 chr12:51779418-51779468 1.0892

12 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr12:51798915-51798965 2.1222 chr12:51801042-51801092 1.9277 chr12:51803860-51803910 3.0753 chr12:51803860-51803910 1.6408 51803885 12.16 chr12:52357486-52457486 chr12:55719156-55819156 chr12:67316997-67416997 chr12:70293866-70393866 chr12:74661784-74814784 chr12:74706859-74706909 3.1846 chr12:74706859-74706909 2.5767 74706884 12.17 chr12:76677664-76777664 chr12:78537258-78637258 chr12:79784162-79884162 chr12:84682551-84782551 chr12:94637004-94737004 chr12:94664042-94664092 1.6052 chr12:94663989-94664039 2.1013 94664041 12.18 chr12:94681638-94681688 1.4936 chr12:94702263-94702313 1.6520 chr12:95039691-95346691 chr12:95093130-95093180 2.1684 chr12:95134126-95134176 3.2965 chr12:95134073-95134123 2.8402 95134125 12.19 chr12:97439870-97539870 chr12:102984507-103084507 chr12:103063860-103063910 2.4424 chr12:103063860-103063910 2.3516 103063885 12.20 chr12:103073886-103073936 2.1348 chr12:105939792-106039792 chr12:115939020-116141020 chr12:116019939-116019989 2.5786 chr12:116022299-116022349 2.3159 chr12:116030745-116030795 3.8569 chr12:116030798-116030848 3.1746 116030797 12.21 chr12:116062613-116062663 3.9152 chr12:116062454-116062504 3.3377 116062559 12.22 chr12:116088149-116088199 4.2616 chr12:116113227-116113277 4.0887 chr12:116113227-116113277 3.1225 116113252 12.23 chr12:122561551-122661551 chr13:30157668-30257668 chr13:30185469-30185519 2.0287 chr13:30218105-30218155 1.3125 chr13:30218105-30218155 1.5074 30218130 13.01 chr13:40026734-40188734 chr13:42445361-42545361 chr13:42477491-42477541 3.2367 chr13:42477389-42477439 3.9282 42477465 13.02 chr13:76957859-77064859 chr13:76980246-76980296 3.7607 chr13:76980246-76980296 3.6275 76980271 13.03 chr13:76988580-76988630 3.2055 chr13:76988507-76988557 3.0723 76988569 13.04 chr13:99382319-99482319 chr13:100816707-100916707 chr13:100848602-100848652 1.7226 chr13:100848428-100848478 1.6385 100848540 13.05 chr13:100849011-100849061 2.0482 chr13:109186915-109286915 chr13:109194274-109194324 4.0610 chr13:109194221-109194271 3.4506 109194273 13.06 chr13:110315417-110415417 chr13:110359045-110359095 2.1181 chr14:23057119-23157119 chr14:23118476-23118526 1.5168 chr14:23118907-23118957 3.7650 chr14:30515340-30615340 chr14:34364604-34464604 chr14:34893695-34993695 chr14:34911832-34911882 2.6670 chr14:34913625-34913675 2.9473 chr14:34913519-34913569 2.6705 34913597 14.01 chr14:34929925-34929975 3.9213 chr14:34929925-34929975 3.3450 34929950 14.02 chr14:34937376-34937426 2.7734 chr14:34937376-34937426 1.9116 34937401 14.03 chr14:34942871-34942921 3.5957 chr14:34942765-34942815 3.2543 34942843 14.04 chr14:52437460-52537460 chr14:52497622-52497672 3.2283 chr14:52497622-52497672 3.8583 52497647 14.05 chr14:53443362-53543362 chr14:53499737-53499787 1.5283 chr14:58675151-58775151 chr14:58764327-58764377 3.1029 chr14:58764168-58764218 1.9314 58764273 14.06 chr14:58774936-58774986 2.4921 chr14:64190945-64290945 chr14:64216633-64216683 1.5686 chr14:64233261-64233311 2.8996 chr14:64233261-64233311 3.1203 64233286 14.07 chr14:64259574-64259624 1.8786 chr14:64286570-64286620 2.7981 chr14:64286570-64286620 2.8529 64286595 14.08 chr14:75064744-75164744 chr14:75096099-75096149 1.7897 chr14:75096258-75096308 2.3408 75096204 14.09 chr14:75098351-75098401 1.7875 chr14:75098404-75098454 2.2188 75098403 14.10 chr14:75115777-75115827 1.7468 chr14:75115777-75115827 3.0580 75115802 14.11 chr14:77889845-78039845 chr14:77938186-77938236 2.0652 chr14:78765434-78865434 chr14:80441621-80541621 chr14:80537530-80537580 3.1867 chr14:80537530-80537580 1.9011 80537555 14.12 chr14:94098479-94198479 chr14:94106621-94106671 2.9487 chr14:94106621-94106671 1.9866 94106646 14.13 chr14:94134684-94134734 2.8697 chr14:94135264-94135314 3.0582 chr14:94135264-94135314 3.2000 94135289 14.14 chr14:94136851-94136901 1.8038 chr15:53906127-54123127 chr15:53977061-53977111 2.4977 chr15:53987414-53987464 1.9631 chr15:53987414-53987464 2.1829 53987439 15.01 chr15:53988836-53988886 4.2818 chr15:53988836-53988886 4.0310 53988861 15.02 chr15:53995641-53995691 3.7362 chr15:53995836-53995886 3.9017 53995764 15.03 chr15:54120199-54120249 3.1927 chr15:54120146-54120196 2.7188 54120198 15.04 chr15:63821640-63921640 chr15:66608645-66778645 chr15:66657720-66657770 2.3285 chr15:66657773-66657823 2.6819 66657772 15.05 chr15:66673536-66673586 4.6979 chr15:66673483-66673533 2.9442 66673535 15.06 chr15:66720723-66720773 2.5929 chr15:66720776-66720826 1.8431 66720775 15.07 chr15:68126212-68226212 chr15:68166401-68166451 3.4995 chr15:68171416-68171466 2.8024 chr15:68174080-68174130 2.5031 chr15:68177841-68177891 1.5902 chr15:70227180-70327180 chr15:70234695-70234745 1.9432 chr15:70234536-70234586 2.0025 70234641 15.08 chr15:70235013-70235063 2.6361 chr15:70243617-70243667 3.9074 chr15:70243617-70243667 2.9920 70243642 15.09 chr15:70247816-70247866 2.3272 chr15:70247763-70247813 2.6359 70247815 15.10 chr15:70248293-70248343 2.2354 chr15:70282938-70282988 0.9347 chr15:70303651-70303701 1.7975 chr15:72754930-72854930 chr15:72776130-72776180 2.8190 chr15:72776130-72776180 2.4376 72776155 15.11 chr15:75211000-75311000

13 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr15:81694472-81794472 chr15:81723849-81723899 3.1615 chr15:81723743-81723793 1.8268 81723821 15.12 chr15:81745730-81745780 2.5344 chr15:81745808-81745858 3.8933 81745794 15.13 chr15:81748730-81748780 1.3929 chr15:81752218-81752268 2.4054 chr15:81752271-81752321 1.9324 81752270 15.14 chr15:81771141-81771191 1.4761 chr15:83674874-84093874 chr15:83675551-83675601 2.4757 chr15:83675551-83675601 2.4307 83675576 15.15 chr15:83675922-83675972 1.4104 chr15:83688601-83688651 2.0446 chr15:83688709-83688759 2.5569 83688680 15.16 chr15:83702596-83702646 2.0237 chr15:83757999-83758049 2.2586 chr15:83757999-83758049 2.0981 83758024 15.17 chr15:83822249-83822299 3.3444 chr15:83822143-83822193 2.9295 83822221 15.18 chr15:83878474-83878524 1.5621 chr15:83881363-83881413 3.2173 chr15:83887427-83887477 2.2812 chr15:83907771-83907821 3.7029 chr15:83910219-83910269 3.2845 chr15:83923303-83923353 3.0327 chr15:83923462-83923512 2.2842 83923408 15.19 chr15:83924713-83924763 2.1102 chr15:83932393-83932443 4.3870 chr15:83932446-83932496 3.1347 83932445 15.20 chr15:83960307-83960357 3.0691 chr15:83960254-83960304 3.7338 83960306 15.21 chr15:83990291-83990341 3.5471 chr15:83990291-83990341 3.0171 83990316 15.22 chr15:84017088-84017138 2.8458 chr15:84069450-84069500 1.8579 chr15:84069450-84069500 1.7912 84069475 15.23 chr15:86550665-86650665 chr15:87207627-87482627 chr15:87428258-87428308 3.6634 chr15:87428045-87428095 3.4014 87428177 15.24 chr15:87442709-87442759 2.6316 chr15:87442709-87442759 1.9627 87442734 15.25 chr15:87445831-87445881 1.9253 chr15:87448889-87448939 1.9561 chr15:87462144-87462194 1.9127 chr15:87462144-87462194 2.8123 87462169 15.26 chr15:87481193-87481243 1.6967 chr15:88479155-88579155 chr15:88509876-88509926 2.0115 chr15:88535950-88536000 1.7552 chr15:89249109-89349109 chr15:89279817-89279867 2.2561 chr15:89279817-89279867 1.3751 89279842 15.27 chr15:91175000-91275000 chr15:91248051-91248101 1.9393 chr16:8748991-8848991 chr16:9043037-9143037 chr16:9074316-9074366 2.1964 chr16:9074171-9074221 2.6237 9074269 16.01 chr16:19585000-19854000 chr16:19750257-19750307 3.3127 chr16:19750560-19750610 2.3793 55138662 16.02 chr16:49283485-49390485 chr16:49291342-49291392 1.8374 chr16:55003895-55323895 chr16:55076147-55076197 2.9440 chr16:55138663-55138713 3.7703 chr16:55138610-55138660 3.6970 55198687 16.03 chr16:55198741-55198791 3.3530 chr16:55198582-55198632 2.9196 55199572 16.04 chr16:55199547-55199597 2.4658 chr16:55199547-55199597 2.6483 55201938 16.05 chr16:55201913-55201963 2.5671 chr16:55201913-55201963 2.5512 55224514 16.06 chr16:55202603-55202653 1.6031 chr16:55217946-55217996 2.1816 chr16:55224436-55224486 2.3262 chr16:55224542-55224592 1.2208 55224938 16.07 chr16:55224913-55224963 2.2159 chr16:55225491-55225541 2.9038 chr16:55227583-55227633 2.9305 chr16:55227636-55227686 1.9129 55227635 16.08 chr16:55228646-55228696 1.8789 chr16:55243451-55243501 2.0419 chr16:55245918-55245968 1.4469 chr16:55245918-55245968 2.5030 55245943 16.09 chr16:55249501-55249551 1.3376 chr16:55270029-55270079 3.0719 chr16:55270506-55270556 3.5716 chr16:55270453-55270503 2.8517 55270505 16.10 chr16:55273644-55273694 1.7626 chr16:55273591-55273641 2.0045 55273643 16.11 chr16:55277096-55277146 1.6870 chr16:55276904-55276954 1.8363 55277025 16.12 chr16:65715370-65815370 chr16:65765124-65765174 2.3290 chr16:65765495-65765545 2.2930 65765335 16.13 chr16:65798360-65798410 1.7734 chr16:67278695-67378695 chr16:67307032-67307082 1.8468 chr16:67307032-67307082 2.6275 67307057 16.14 chr16:67347600-67347650 1.7984 chr16:67347547-67347597 1.9560 67347599 16.15 chr16:67366974-67367024 3.9668 chr16:67366974-67367024 2.5673 67366999 16.16 chr16:78142112-78242112 chr16:78203775-78203825 2.3477 chr16:78223970-78224020 2.4483 chr16:78223970-78224020 2.4145 78223995 16.17 chr16:82440172-82590172 chr16:82510672-82510722 2.9196 chr16:82510937-82510987 2.0480 82510830 16.18 chr16:82519625-82519675 1.6371 chr16:82519784-82519834 2.4984 82519730 16.19 chr16:83361112-83461112 chr16:83413837-83413887 2.3916 chr16:83423722-83423772 2.1458 chr16:83423881-83423931 3.0218 83423827 16.20 chr16:84440274-84540274 chr16:84531449-84531499 1.9771 chr17:5213720-5313720 chr17:5277677-5277727 2.7319 chr17:5277889-5277939 2.7666 5277808 17.01 chr17:7481642-7581642 chr17:15059369-15159369 chr17:21077910-21187910 chr17:21147687-21147737 2.2045 chr17:24143934-24243934 chr17:24160079-24160129 2.2725 chr17:24160133-24160183 2.1565 24160131 17.02 chr17:26007000-26107000 chr17:26056941-26056991 2.4563 chr17:26396242-26496242 chr17:29556408-29656408 chr17:31391600-31491600 chr17:31478913-31478963 1.9605 chr17:31478724-31478774 2.0213 31478844 17.03 chr17:35861341-35961341 chr17:35894473-35894523 1.5362 chr17:35895993-35896043 2.2451 chr17:35896152-35896202 1.5469 35896098 17.04 chr17:35920168-35920218 2.1171 chr17:35920009-35920059 1.7827 35920114 17.05 chr17:40530466-40630466 chr17:40581958-40582008 2.3791 chr17:42636206-42745206 chr17:55275078-55375078 chr17:55277737-55277787 1.6984 chr17:55285803-55285853 2.7816 chr17:56060014-56160014 chr17:56103803-56103853 4.0556 chr17:56103714-56103764 3.6715 56103784 17.06 chr17:59511208-59611208 chr17:59513518-59513568 2.1152 chr17:59513607-59513657 2.5485 59513588 17.07 chr17:59519247-59519297 2.1529

14 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr17:59560177-59560227 3.9801 chr17:59560230-59560280 2.8667 59560229 17.08 chr17:59589022-59589072 1.6515 chr17:59602227-59602277 1.7254 chr17:60938227-61038227 chr17:62754385-62854385 chr17:62817243-62817293 2.0819 chr17:62817296-62817346 2.0006 62817295 17.09 chr17:62848754-62848804 1.7167 chr17:68050000-68150000 chr17:68096939-68096989 3.3265 chr17:68096939-68096989 3.2510 68096964 17.10 chr17:68117306-68117356 3.1089 chr17:68117306-68117356 3.4921 68117331 17.11 chr17:68130718-68130768 1.8122 chr17:68650952-68790952 chr17:68723578-68723628 3.3932 chr17:68723472-68723522 3.3880 68723550 17.12 chr17:68732944-68732994 4.4133 chr17:68732944-68732994 2.8421 68732969 17.13 chr17:68743800-68743850 2.7333 chr17:68743800-68743850 2.5557 68743825 17.14 chr17:68758583-68758633 2.3422 chr17:72043524-72143524 chr17:72054309-72054359 2.0065 chr17:72058806-72058856 2.0323 chr17:72065126-72065176 3.0644 chr17:72065126-72065176 3.8984 72065151 17.15 chr17:72092353-72092403 2.0695 chr17:72134031-72134081 1.5138 chr17:72598616-72698616 chr17:72632314-72632364 2.3237 chr17:72633247-72633297 2.3303 chr17:72634064-72634114 2.1449 chr17:72634064-72634114 1.8400 72634089 17.16 chr17:72635828-72635878 2.1019 chr17:73671871-73771871 chr17:73706678-73706728 1.5170 chr17:73706678-73706728 1.2992 73706703 17.17 chr17:73719040-73719090 3.0140 chr17:73718881-73718931 1.5661 73718986 17.18 chr17:73721086-73721136 2.7821 chr17:73721245-73721295 1.7829 73721191 17.19 chr17:73817753-73917753 chr17:73859556-73859606 2.3007 chr17:73916772-73916822 1.5341 chr17:73917039-73917089 1.5382 73916931 17.20 chr17:75574242-75674242 chr17:75581876-75581926 2.8621 chr17:75581929-75581979 3.9000 75581928 17.21 chr17:75652520-75652570 5.1129 chr17:75652573-75652623 3.9899 75652572 17.22 chr17:75657186-75657236 2.4121 chr17:76573556-76706556 chr17:76632304-76632354 4.1120 chr17:76632357-76632407 4.1419 76632356 17.23 chr17:76637839-76637889 2.0597 chr17:76638634-76638684 1.3092 chr17:76642968-76643018 2.0359 chr17:76644579-76644629 1.8024 chr17:76645920-76645970 2.6755 chr17:76645920-76645970 3.4635 76645945 17.24 chr17:76652108-76652158 3.7148 chr17:76652108-76652158 3.2897 76652133 17.25 chr17:76654281-76654331 2.5152 chr17:76654281-76654331 2.3194 76654306 17.26 chr17:76669632-76669682 2.3297 chr17:76685445-76685495 2.4156 chr17:76685445-76685495 1.7835 76685470 17.27 chr17:76687561-76687611 2.0574 chr17:76704138-76704188 1.5930 chr17:77566969-77666969 chr17:77612844-77612894 1.7728 chr17:77612632-77612682 1.3384 77612763 17.28 chr17:77652212-77652262 1.8262 chr17:77665208-77665258 3.1013 chr17:77665314-77665364 3.3208 77665286 17.29 chr18:3352071-3452071 chr18:3357961-3358011 1.9465 chr18:3357908-3357958 2.0525 3357960 18.01 chr18:3437109-3437159 2.4097 chr18:3440351-3440401 2.5227 chr18:8099000-8199000 chr18:8131385-8131435 2.3269 chr18:44681079-44781079 chr18:46760610-46860610 chr18:46811551-46811601 1.9734 chr18:54988379-55088379 chr18:55056738-55056788 2.1037 chr18:55056738-55056788 2.2559 55056763 18.02 chr18:55668216-55768216 chr18:55684925-55684975 2.8298 chr18:55684925-55684975 1.9806 55684950 18.03 chr18:55717711-55717761 1.6812 chr18:55741476-55741526 2.4359 chr18:55741635-55741685 2.4941 55741581 18.04 chr18:59430094-59530094 chr18:59461781-59461831 2.8489 chr18:59479419-59479469 2.8406 chr18:59479419-59479469 1.8795 59479444 18.05 chr18:59498665-59498715 1.7307 chr18:59498718-59498768 2.0828 59498717 18.06 chr18:71075160-71175160 chr19:564227-664227 chr19:2377256-2477256 chr19:4148107-4248107 chr19:6432036-6532036 chr19:8285010-8385010 chr19:8317541-8317591 2.9968 chr19:8326838-8326888 3.7946 chr19:8326838-8326888 3.7807 8326863 19.01 chr19:8373395-8373445 3.9052 chr19:8373395-8373445 3.1514 8373420 19.02 chr19:12713309-12813309 chr19:12721822-12721872 3.0212 chr19:12722352-12722402 3.6611 chr19:12722246-12722296 3.4994 12722324 19.03 chr19:13072281-13172281 chr19:13106727-13106777 2.0033 chr19:13106727-13106777 2.1502 13106752 19.04 chr19:18125839-18225839 chr19:18125945-18125995 2.5374 chr19:18125945-18125995 2.4145 18125970 19.05 chr19:18186991-18187041 1.8842 chr19:18186991-18187041 2.2687 18187016 19.06 chr19:19437469-19537469 chr19:20586217-20686217 chr19:40059723-40159723 chr19:41551390-41651390 chr19:43468297-43568297 chr19:43558291-43558341 1.9503 chr19:43558344-43558394 1.7671 43558343 19.07 chr19:45573738-45673738 chr19:46501656-46601656 chr19:48927249-49027249 chr19:48936089-48936139 2.0749 chr19:48945564-48945614 2.1777 chr19:48945511-48945561 2.0499 48945563 19.08 chr19:48982766-48982816 2.5792 chr19:50324394-50424394 chr19:50349529-50349579 3.2502 chr19:50349582-50349632 3.1655 50349581 19.09 chr19:50367524-50367574 2.7675 chr19:50367524-50367574 2.5673 50367549 19.10 chr19:50368389-50368439 1.8154 chr19:50370804-50370854 3.9463 chr19:50370910-50370960 3.4780 50370882 19.11 chr19:50613092-50713092 chr19:50624747-50624797 2.1150 chr19:52376291-52476291 chr19:52437652-52437702 2.1134 chr19:52437493-52437543 1.3729 52437598 19.12 chr19:55999982-56099982 chr19:56091998-56092048 2.2491 chr19:56091998-56092048 1.8382 56092023 19.13

15 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chr19:58666089-58776089 chr19:60523626-60623626 chr19:627032-627082 1.7543 chr20:4565068-4665068 chr20:4642008-4642058 1.7883 chr20:5474672-5589672 chr20:5586425-5586475 3.3453 chr20:5586425-5586475 3.6308 5586450 20.01 chr20:6647206-6747206 chr20:6688084-6688134 1.5324 chr20:7898393-7998393 chr20:7951923-7951973 2.2144 chr20:7951923-7951973 1.7190 7951948 20.02 chr20:10097476-10197476 chr20:10157016-10157066 2.0505 chr20:12887846-12987846 chr20:12895825-12895875 1.5656 chr20:12958795-12958845 1.9283 chr20:12963634-12963684 1.6523 chr20:22928301-23028301 chr20:22968455-22968505 2.9259 chr20:22968996-22969046 2.9461 chr20:22968996-22969046 3.2831 22969021 20.03 chr20:22979672-22979722 1.5151 chr20:23007381-23007431 2.6980 chr20:23007381-23007431 2.3532 23007406 20.04 chr20:23017588-23017638 2.0750 chr20:23019455-23019505 4.0041 chr20:23019353-23019403 3.2197 23019429 20.05 chr20:23023844-23023894 2.0528 chr20:23023791-23023841 2.1065 23023843 20.06 chr20:24934616-25037616 chr20:24946202-24946252 1.7898 chr20:24946202-24946252 1.6686 24946227 20.07 chr20:24951974-24952024 2.2609 chr20:24968702-24968752 1.9906 chr20:24976836-24976886 3.0805 chr20:24976836-24976886 2.1564 24976861 20.08 chr20:24977241-24977291 3.4406 chr20:24977294-24977344 2.2763 24977293 20.09 chr20:25126705-25226705 chr20:25145138-25145188 1.1693 chr20:25154354-25154404 2.0463 chr20:25154248-25154298 1.2381 25154326 20.10 chr20:25155202-25155252 3.2221 chr20:25166231-25166281 1.5769 chr20:25166858-25166908 2.0458 chr20:25205298-25205348 3.0204 chr20:25205722-25205772 2.5753 chr20:25206529-25206579 3.0313 chr20:25206411-25206461 2.1599 25206495 20.11 chr20:33666262-33766262 chr20:34378857-34563857 chr20:34415561-34415611 2.0777 chr20:34415561-34415611 1.2873 34415586 20.12 chr20:47982933-48082933 chr20:48190782-48290782 chr20:52173931-52273931 chr20:55669947-55769947 chr20:55701423-55701473 1.7963 chr20:55701476-55701526 2.5242 55701475 20.13 chr20:55702059-55702109 2.1689 chr20:55703299-55703349 1.7429 chr21:27089599-27189599 chr21:29543090-29643090 chr21:29553269-29553319 2.1126 chr21:29553269-29553319 1.9864 29553294 21.01 chr21:33270162-33370162 chr21:37611728-37761728 chr21:37633149-37633199 1.7541 chr21:37687347-37687397 3.7263 chr21:37687455-37687505 2.8612 37687426 21.02 chr21:41751948-41851948 chr21:42010318-42110318 chr21:42054897-42054947 1.7272 chr21:42077353-42077403 2.3010 chr21:42088807-42088857 2.4010 chr21:42089754-42089804 2.4171 chr21:42098265-42098315 2.4576 chr21:42108392-42108442 2.7150 chr21:42109836-42109886 1.9671 chr21:45268942-45368942 chr21:45272739-45272789 2.2535 chr21:45288003-45288053 1.7768 chr21:45294729-45294779 2.7603 chr21:45315003-45315053 2.7167 chr21:45314791-45314841 2.5130 45314922 21.03 chr21:45316222-45316272 1.9357 chr21:45316381-45316431 1.2869 45316327 21.04 chr21:45361779-45361829 1.8710 chr22:17791280-17891280 chr22:17817772-17817822 1.2589 chr22:17817825-17817875 2.6247 17817824 22.01 chr22:17844912-17844962 3.0702 chr22:18328863-18428863 chr22:18339624-18339674 1.9026 chr22:18339730-18339780 1.9552 18339702 22.02 chr22:18346783-18346833 0.8100 chr22:18360853-18360903 2.1461 chr22:18372659-18372709 3.7520 chr22:18372553-18372603 3.1364 18372631 22.03 chr22:25099655-25254655 chr22:25136831-25136881 2.9527 chr22:25137318-25137368 2.5172 chr22:25248306-25248356 2.7621 chr22:29067486-29167486 chr22:29129568-29129618 3.8964 chr22:29134939-29134989 2.3655 chr22:29134939-29134989 2.1951 29134964 22.04 chr22:29141281-29141331 3.0119 chr22:29141010-29141060 1.5822 29141171 22.05 chr22:29143289-29143339 2.9570 chr22:29143819-29143869 3.0685 chr22:30301364-30401364 chr22:30306812-30306862 3.6444 chr22:30306812-30306862 2.8636 30306837 22.06 chr22:30326942-30326992 2.2595 chr22:30326942-30326992 1.6787 30326967 22.07 chr22:30367420-30367470 1.6566 chr22:30367420-30367470 1.6818 30367445 22.08 chr22:35690201-35790201 chr22:35715799-35715849 2.8019 chr22:37176816-37276816 chr22:37177472-37177522 2.8636 chrX:14997840-15097840 chrX:15047647-15047697 1.5902 chrX:15048315-15048365 3.1421 chrX:15048315-15048365 3.3878 15048340 X.01 chrX:17103199-17203199 chrX:27474000-27574000 chrX:46402628-46502628 chrX:73567464-73667464 chrX:86528961-86628961 chrX:105177463-105277463 chrX:106762162-106875162 chrX:106767747-106767797 3.8801 chrX:106768177-106768227 3.3914 chrX:106791108-106791158 2.3761 chrX:106797165-106797215 2.1849 chrX:106797377-106797427 3.0422 106797296 X.02

16 Bolton_et_al._Supplement

Chromosomal_region_tiled Mpeak_peak#1 Mpeak_Value#1 Mpeak_peak#2 Mpeak_Value#2 Validated Mpeak_peaks_mean ARBR chrX:106817250-106817300 2.7046 chrX:106817250-106817300 2.4617 106817275 X.03 chrX:109002487-109102487 chrX:117211923-117311923 chrX:122506221-122606221 chrX:133357000-133457000 chrX:133412976-133413026 2.1010 chrX:133428919-133428969 1.7373 chrX:133429954-133430004 3.0712 chrX:133430113-133430163 2.9633 133430059 X.04 chrX:133433312-133433362 1.8553 chrX:133434025-133434075 3.4722 chrX:133434131-133434181 2.4041 133434103 X.05 chrX:133440360-133440410 1.1865 chrX:133468033-133568033 chrX:133482567-133482617 2.2294 chrX:133536240-133536290 3.1464 chrX:133536293-133536343 2.9124 133536292 X.06 chrX:133548013-133548063 2.9640 chrX:133547777-133547827 3.4000 133547920 X.07 chrX:138400372-138500372 chrX:138498143-138498193 1.4143 chrX:138589967-138689967 chrX:149234287-149334287 chrX:149772336-149872336 chrX:149829012-149829062 4.2998 chrX:149829012-149829062 3.4951 149829037 X.08 chrX:151620078-151720078 chrX:151672589-151672639 2.0306 chrX:151674085-151674135 3.3262 chrX:151674085-151674135 2.6847 151674110 X.09 chrX:151711176-151711226 3.1061 chrX:151711176-151711226 2.6249 151711201 X.10 chrX:151716363-151716413 2.3151 chrX:151718017-151718067 2.8946 chrX:151718017-151718067 3.1738 151718042 X.11

17 Bolton_et_al._Supplement

Supplemental Table 2. Primers used for PCR cloning and mutating wild-type ARBRs Nearest Reporter ARBR FORWARD PRIMER REVERSE PRIMER ARG Activity Wild-type ARBRs 1.25 TAGGTACCGATTGCTTTTCTAGCCGCAG ATCTCGAGGGCGTTGATGAGTGCAG Induced Induced 1.41 GCTGCAGGTACCGTCACACGACGTGAACTGGGGCGGT TGCAGCCTCGAGCGGTTCTGCTGTTCAGTGACCAGCTT Induced Unresponsive 1.48 GCTGCAGGTACCAATGCCGAGCACAACCACCCCAAGCC TGCACTCGAGCTCATCACCCTGCTGTCCAGAGAAC Induced Induced 2.16 GCTGCAGGTACCTGCAGGGGTCCTCTAGGTC TGCACTCGAGCACAGTGTAAAAAGGGCCAAGTAC Induced Induced 2.32 GCTGCAGGTACCGTGAGGGTGTAGGATGAGGCCCGCT TGCAGCCTCGAGGGACACCCGGTGTTCTGCAACCCAT Induced Induced 2.33 GCTGCAGGTACCGGTCAAATGCTGGGTGCGTTTCAAG TGCAGCCTCGAGACTGGGGTGTGAAGAAGCACAGCTT Induced Induced 4.02 TAGGTACCTTCATCTTGAAGGCTGCC ATCTCGAGCCAAGGCCCAGGGTGTG Induced Induced 4.29 TAGGTACCAGCCAACTTGGGCAGATAG ATCTCGAGGAAAGTGCCTGCATAGC Induced Induced 5.18 GCTGCAGGTACCTTATTTGAGAAGGGAGGATATCACT TGCAGCCTCGAGTTGTGTCAGTGCTCGGTTCCTAAGC Induced Induced 6.14 GCTGCAGGTACCTTGGTAGAGAAAGAAATAAACAAGTT TGCACTCGAGAAATAGACACTTACCAGAGCTAATGTC Induced Induced 6.17 GCTGCAGGTACCGTTTAGAACCTAAAGACGGGGAGTGGG TGCAGCCTCGAGCTGGGCTGCTGGGGCTGTCTGCACCC Induced Induced 6.18 GCTGCAGGTACCTCATTTCAATACACCCAATATTTATTG TGCAGCCTCGAGGAACAAAGCATTTATATCGCACGTTTACC Induced Induced 6.35 GTACCCGGACAAAATGTTCTC TCGAGAGAACATTTTGTCCGG Induced Induced 7.07 GCTGCAGGTACCTATTTTTTCAAACTTTCCCATCAGTTTG TGCAGCCTCGAGATAAAGCCCCTGGCCTCAGTTTT Induced Unresponsive 7.08 GCTGCAGGTACCGCCACCCTGGGTCCCCCACCAGTCT TGCAGCCTCGAGCAGAGAATCCGCAGGAAATCCCTGT Induced Induced 7.11 GCTGCAGGTACCTCCTGTAACCTCTCCAGGAGGGAAAAGC TGCAGCCTCGAGCTGCCCCCTGCCTGGGTCCACCCCTA Induced Induced 9.06 GCTGCAGGTACCTTTGTCTCCAGCCCTGGGCAGACAT TGCAGCCTCGAGCACCCATGGGGGACCTGTGCCTCGTGCC Induced Induced 12.11 TAGGTACCTCTCCAGAGGGATTTTCC ATCTCGAGATCAGTGACTTGTGCG Induced Induced 12.16 TAGGTACCTGAGTTCAAGATCTTCTCC ATCTCGAGAAAGTTGCCTGAGCCAG Induced Induced 20.03 GCTGCAGGTACCAACTAGGAAAGGAAGGGGCGGGGCA TGCAGCCTCGAGTCAATACTCCCATTCTAGGCATTTT Induced Induced 21.03 TAGGTACCATCAGTTCGTCCTCTCTC ATCTCGAGAGGTGACCAATATTCGGTG Induced Induced X.11 TAGGTACCAGCTATCCTAGCAAAGTC ATCTCGAGGCCAATAAGACAATCTCAGTG Induced Induced 1.23 TAGGTACCAGTTCTGTGGAGGGAATG ATCTCGAGGAACAGCTTCCCCAGTC Repressed Induced 1.24 GCTGCAGGTACCACATGGCCTTAGATATCTTTTCCTC TGCAGCCTCGAGCTCGGCCACTGTCCAGGAAGAGGCA Repressed Unresponsive 3.03 GCTGCAGGTACCAACCATATGCATCAGAGCTGGGGCT TGCAGCCTCGAGGTCCCCATCTCACAGACATCGTCTC Repressed Induced 3.11 TAGGTACCTGTCAAGATGCCCTGTAC ATCTCGAGGGAAGTTGCTATGCAGC Repressed Induced 4.16 GCTGCAGGTACCCTCAGAGATACCAGTAACCGCCTG ATCTCGAGGTTCCAAGATTTCAAAGAGAGAAAGG Repressed Unresponsive 19.01 GCTGCAGGTACCCCTAAAGGTCTCAGAAGCTCAATTT TGCAGCCTCGAGGACTCAGGTTCAAGGAAGAGCATGA Repressed Induced Mutated ARBRs m1.48 CCCAGACTTCTATGTCCTGACCAGCTGCCAATCACCTTG GACATAGAAGTCTGGGCAACTCCCAGCCCTCCCCTGCC Induced Unresponsive m2.33 CTAGATTGCATTTTTTCCTCAGGTCTCTGAAATATCAGG CCTGATATTTCAGAGACCTGAGGAAAAAATGCAATCTAG Induced Unresponsive m5.18 CAGAGAGCTTGAGCTTAACGTGAAGCTACCGGTGCTGTTGGG CCCAACAGCACCGGTAGCTTCACGTTAAGCTCAAGCTCTCTG Induced Unresponsive m6.17 CATTCCGGTCCCAGCGTATTAAACTAGACCAGCCTTTTTGAG CTCAAAAAGGCTGGTCTAGTTTAATACGCTGGGACCGGAATG Induced Unresponsive m6.18 TACCTTTCTCACGGCGGAGCGTTCGGCCTGTCTCATATTC TACCTTTCTCACGGCGGAGCGTTCGGCCTGTCTCATATTC Induced Unresponsive m6.35 GTACCCGGGTAAAATTCTCTC TCGAGAGAGAATTTTACCCGG Induced Unresponsive Modestly m7.08#1 CGTCCTGGATACAGTAGAGGTTTCCCAGATGTTTAC GTAAACATCTGGGAAACCTCTACTGTATCCAGGACG Induced Induced Modestly m7.08#2 CTGGACTGCTTGCACGTCCATACCTGTGCCATTCTTGG CCAAGAATGGCACAGGTATGGACGTGCAAGCAGTCCAG Induced Induced m7.08 combination of m7.08#1 and m7.08#2 Induced Unresponsive m7.11 CCTTGAGATACAGGTCCGACGTGTCCTGTCTACGCA TGCGTAGACAGGACACGTCGGACCTGTATCTCAAGG Induced Unresponsive m9.06 CGTGAACTGGGAAAGCACCAAACGCTCTACTCAAAAGCC GGCTTTTGAGTAGAGCGTTTGGTGCTTTCCCAGTTCACG Induced Unresponsive m19.01 CACTGGTTTCGATGTGCCATTACATAGTCCTAACAACC CATCGAAACCAGTGACTGGCCTCTACCGCCCCCAGC Repressed Unresponsive

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Supplemental Table 3. Real-time quantitative PCR (qPCR) primers for androgen-responsive gene (ARG) validation and expression profiling HUGO Gene Symbol ENTREZ GeneID Forward Primer Reverse Primer Response to R1881 in HPr-1AR RPL19 6143 ATGTATCACAGCCTGTACCTG TTCTTGGTCTCTTCCTCCTTG Control, Unresponsive gene SNAI2 6591 AGCTACCCAATGGCCTCTCT GGGTCTGAAAGCTTGGACTG Repressed ELL2 22936 TCAAAGAGACTGGCCTGGAT CAAAAGCCGTTTCTGAGGAG Induced MAF 4094 CAGAACTGGCAATGAGCAAC CCGGTTCCTTTTTCACTTCA Unresponsive gene CXCR7 57007 CCAGTCTGGGTGGTCAGTCT CTCATGCACGTGAGGAAGAA Induced FKBP5 2289 AGGCTGCAAGACTGCAGATC CTTGCCCATTGCTTTATTGG Induced DKK1 22943 CCTTGGATGGGTATTCCAGA CAGTCTGATGACCGGAGACA Repressed FST 10468 TGTGCCCTGACAGTAAGTCG CCGAAATGGAGTTGCAAGAT Repressed PHLDA1 22822 TCACTGTGGTGATGGCAGAG GATGGCCTGACGATTCTTGT Repressed FGFBP1 9982 AAGGACACTCTGGGCAACAC GAGAGAGATGCCCTCCTCCT Repressed NUP88 4927 TCGTGCTAGAAGGGGAAGAA CAGATGCCAGTTTCAAAGCA Unresponsive gene MYC 4609 CCGAGGAGAATGTCAAGAGG TAACTACCTTGGGGGCCTTT Repressed TP73L 8626 GAAACGTACAGGCAACAGCA CACAGAAGGCAGCTTGTTCA Repressed AREG 374 GTGTGGGGAAAAGTCCATGA AACAGCAACAGCTGTGAGGA Repressed RIPK4 54101 GCTCATGATCTGGACGTGAA TCGGAGAGGCTGTAGTCGTT Induced ADARB1 104 TCGTGGAGCCCATTTACTTC CAAAGGCTTGTTGAGGGTGT Induced AADAT 51166 TTAATGCTCCCTGGAAATGC GAAGGCCACATCCATCTGTT Unresponsive gene ARL4C 10123 CCCTGCATATCGTCATGTTG CCGTTGCTCAGCTTGATCTT Repressed ANTXR2 118429 CATTAACTGGAGACAGAGGC TTCAAGCCTCCTGCTTTCTG Repressed DUSP5 1847 AAGGTCCTGGTCCACTGTGA GAGACCATGCTCCTCCTCTG Repressed EDG2 1902 ACAACGAGTCCATTGCCTTC AGATTGCCACCATGACCAAT Repressed ELK3 2004 CTTCTTCACCGCACAGACAC AGTGTGGGGAACTGGAACAG Repressed EPB41L4B 54566 ATGGCTCCAGGTTACGAAGA TGCTATCACTGGGTTGCTTG Induced CYLD 1540 TCCCTTGCCAGAATATGGAG AAGCCATTCTGACCACCATC Induced CORO2B 10391 AGGATGAGATTCGACGGTTG AACAGTTCTTGGGGCTGTTG Induced CYP24A1 1591 GAAGAATGCAGGGGATGAAG TTGGTGTTGAGGCTCTTGTG Repressed BAIAP2 10458 TCAAGCAGAGGCCCTACAGT ATCACACCTGTCGTTGGTCA Induced CXCL1 2919 CACCCCAAGAACATCCAAAG TAACTATGGGGGATGCAGGA Repressed CA2 760 TCTGGAATGTGTGACCTGGA CACCCTCCCCATTGAAGTTA Induced FN1 2335 GATGCTCCCACTAACCTCCA CGGTCAGTCGGTATCCTGTT Induced FOXO1A 2308 CTTGGATGGCATGTTCATTG CTGTGTGGGAAGCTTTGGTT Induced GATA2 2624 TGACGGAGAGCATGAAGATG GGCACATAGGAGGGGTAGGT Induced IRF2BP2 359948 GACACCCATTTTGTGCAGTG TCCACTAGCTCCCTGCTGTT Repressed KIAA1522 57648 TCATACCTCCTCACCCCAAG TGGCGTCAGTGGTAGAAACA Unresponsive gene KLF4 9314 GTCTCTTCGTGCACCCACTT TGCTCAGCACTTCCTCAAGA Induced KCNN4 3783 CATGCAGAGATGCTGTGGTT GAACAGCTGGACCTCTTTGG Repressed KIAA0232 9778 TGAGTTGTTTTCGGCAGATG CTCTTTCTGTCCCTCCCACA Induced TBC1D9B 23061 CCAACCTGAAAGACCGTGAT GAGCTGGGGAAGACTCTGTG Unresponsive gene with ARBR DNMBP 23268 TAAAAAGCACCACACGTCCA GTCAGCTTCGAGTCCAGGTC Repressed KIAA1434 56261 CCTGGAGGAAGATGACGATG TGCAAGCCATAACCACACTC Repressed PLEKHA7 144100 CTCCATCTCTGTGCCTCCAT TCACTGTGACTCGCTCTGCT Induced C7orf40 285958 TGCTGATGCTCTGGCTATTG AGGAACTGGCAGCTAACACG Unresponsive gene MAPKAPK2 9261 TCTGTACGCAGGGAGGAAGT CTGTGAATGCCTGGTCTCCT Induced MGC16121 84848 GAGCAAGGGATCCTGACTTG GGACGAGCTCAATTTCGATG Induced KLHDC8B 200942 GGAGAGCTTTAGCCTTGCAC CACCCCCAATAACAAACAGC Induced MPST 4357 ACATCCCAGGTACCGTGAAC CCACCAGTGGCTTAGACAGG Induced MME 4311 CCGAACCTACAAGGAGTCCA GCAAATGCTGCTTCCACATA Induced MTX1 4580 ACTGGTGCTCCACTGAAGGT CTCTTTTCGAAGGTGGGTGA Unresponsive gene NFKBIA 4792 CTACACCTTGCCTGTGAGCA AGACACGTGTGGCCATTGTA Induced OSBPL11 114885 ACGGAGCTTCTCACTTGCAT CCACAAGATGGTCTGGAGGT Induced FAM84B 157638 GAGTACCTACACGCCCGAGA CCACCTGGAAGTTACCCACA Repressed PAG1 55824 AAAACATGGTGGAGGACTGC AGATTTTGCCTTGCCACTGT Induced CD274 29126 GCTATGGTGGTGCCGACTAC TGCTTGTCCAGATGACTTCG Repressed PLAU 5328 AGCCCCACTACTACGGCTCT CCAGCTCACAATTCCAGTCA Repressed PLEC1 5339 CCAGCTTCGAGGAGATTGAG GATTGGTAGATGCCCTTGGA Repressed PLK2 10769 AAAGTTGGGGACTTCGGTCT CACAGCCATGTCCTTGTTTG Repressed PTHLH 5744 CAAGATTTACGGCGACGATT GGAGAGGGCTTGGAGTTAGG Repressed PRNP 5621 ACAACTTTGTGCACGACTGC ACGCGCTCCATCATCTTAAC Repressed PMVK 10654 TTGGAGCTGATGTCTGTGCT CTTGTAGGTGCTGGTGTCCA Induced TMEM37 140738 TTGTGCGAGGACAAACACTC ACATTAGGGTGAAGCCGATG Induced ZMIZ1 57178 AGAGAGGGACCTGGAGGTGT AAACTCGGAGTGTTGGATGG Repressed GPRC5A 9052 GCCCACATCTACCTCACGAT GGAGCTGAGGATGGTGTCAT Repressed RNF126 55658 ACCAGGAGCACAGAAAATGG AGATGCCGAAAGCAAACTGT Unresponsive gene SLCO2A1 6578 CCAACTTCCTCATTGGTGCT CGGGGAATGGTTTGTAGAGA Induced PRSS23 11098 ACTTACGAAGAGGCCAAGCA CCTGAAGACCCTGAGTCTCG Induced SSX2IP 117178 AAGCAGAGAGAGTATGTGGG GGTGTACCTTTGAAACTTGG Induced

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HUGO Gene Symbol ENTREZ GeneID Forward Primer Reverse Primer Response to R1881 in HPr-1AR ST5 6764 TTACTGCCAAGTGGGAAAGG CGCTCCACCTCATCTAGGAC Induced S100P 6286 GATGCCGTGGATAAATTGCT TTGTGACAGGCAGACGTGAT Induced SLC12A7 10723 GAAAACAGCCCATTCCTCAA TGGGGTTACTGTCCATCTCC Induced SLC16A1 6566 GTCTATGCGGGATTCTTTGG AGGACAGGACAGCATTCCAC Unresponsive gene SLC22A3 6581 TCATAGCCCCATTTCTGCTC TCAGGCAAAAGCATCACAAG Induced GRHL1 29841 CCTCTCACAAGCGAATGGAT GCAATGGGAAGGACATGAGT Induced TIPARP 25976 CCATCAGAAACCCTCAGTGG TCTTGGAAAATGCCTGGAAC Induced TM4SF1 4071 TGCAGGATCTGGCTACTGTG GGTGCTGGCAAAGGTGTAGT Repressed UAP1 6675 AACCAGTTGGAGTGGTTTGC GAAATGGTTGGCAATGTTCC Repressed AKAP13 11214 CAAGTCTGGCCACAGAGTCA TTAAGAGCATCGGACCCATC Induced ACSS1 84532 TGATGAGATCCTGGTGGTGA GGGTCCTCCAAGGTGGTAGT Induced ACSL1 2180 TTGGGAAGGATTCTGGTCTG GTCAGAAGGCCATTGTCGAT Induced AQP3 360 TTGGCTTTGCTGTCACTCTG GTAGATGGGCAGCTTGATCC Induced DDIT4 54541 CCTGGACAGCAGCAACAGT TCACTGAGCAGCTCGAAGTC Repressed BMP2 650 ATGGAAAAGGGCATCCTCTC AGCCACAATCCAGTCATTCC Repressed FOXC1 2296 AGCAGCAGAACTTCCACTCG GGAAGGCCATTTGACAGCTA Induced NSDHL 50814 CTATCCCTGCTGGTGATGGT GGCTCTCTCGCAGCTGTAGT Induced ETNK2 55224 TCACGCTTGTGAAGAACGAG TCTTGCAGAGCAGGTCATTG Induced IL6R 3570 CTCCTGCCAGTTAGCAGTCC AGGCTGCAAGATTCCACAAC Repressed KIAA1727 85462 GTAGCAGCGACCCTGAGAAC GTTCCCTCTGAGCAGTCCAG Induced PCYOX1L 78991 CTACTCACTGGGGGAGTCCA GGACAGCAGAAACGACATCA Induced PGM2L1 283209 CAGAGATGTGTGCGTCACCT AACGCCAGATCAGTCCATTC Induced PTP4A1 7803 ACACACAATCCAACCAATGC AGGCCAATCAAGAACATGGA Unresponsive gene SGK 6446 TGCTGCTGAAATAGCCAGTG CTCCTTGCAGAGTCCGAAGT Induced TFPI2 7980 ACTGTGCTCTGCCAATGTGA ATTGTCATTCCCTCCACAGC Induced TLE3 7090 AATGGTGAGCTTTGGAGCTG AGTACGCTGGTTTTCCTCCA Induced ITGB3 3690 TGGCAGCTGTGTCTGTATCC CCCCGGTCAAACTTCTTACA Unresponsive gene NT5E 4907 CTGGGAGCTTACGATTTTGC GCTGAACCTTGGTGAAGAGC Repressed ADAMTS1 9510 CGTCTCACCAAAGGACAGGT GAGGTGGAATCTGGGCTACA Repressed UCK2 7371 ACAGCTAGCGGCAAGTCTTC CTGCTCCGAGGTAAGGACAC Unresponsive gene with ARBR SEMA3G 56920 GGTGCTGGTGAACAAATGG CACAGCAGGAACACATCCTC Induced HMGB3 3149 ACAACCGAGACAAACCCTTG GTCAACAGGTCCAGCCTCAC Induced SPTLC3 55304 GGCTCGGTTTTGTGTTTCAG GACGTGCTGACTTCTTGTGC Induced C17orf80 55028 GGAGCAAAGGAAATGCAGAG CTGTGACTGAATCCCTGGTG Induced TGFB1 7040 CCACGGAGAAGAACTGCTG CCAGGCTCCAAATGTAGGG Unresponsive gene NEDD4 4734 ATCTCGGGTGCCTATGAATG GTCCAGGCGATTAAAACAGG Induced BIN1 274 CCTGCTGTGGATGGATTACC TTGAAGGGACTCGTAGTGGTG Induced IGFBP3 3486 GTTCCTCAATGTGCTGAGTCC GCTGCCCATACTTATCCACAC Induced LASS6 253782 AAGACGCAATCAGGAGAAGC ATGCCTCGTATTCCACAACC Induced MPHOSPH10 10199 ATGCCCTCTCAAACTTCCAC CACTCACTGGGGCTACTTCC Induced INHBA 3624 AAAGGAGCAGTCGCACAGAC TTGACCTTGCCATCACACTC Repressed CMTM7 112616 ATGATCCTCGCCTTTTACCTG CGCTCTGGTTGTAACTCTTGG Unresponsive gene SEMA4B 10509 TGCAGACGCAGAGAAGAAAC AGGTACACATGGGGCTGAAG Repressed DCBLD2 131566 CCTTCTCCATGCCTCTGTTC TGTAAGGGTTCCACTCTCAGG Repressed ST6GALNAC2 10610 GTGGCCTGTTCAATCTCTCC CATACGGGGCTTTGTGTTG Unresponsive gene PNKD 25953 TCTTCCTCTCTGGCTGTGG AAGCCCAGGTTCTCCTCTG Repressed ARID5B 84159 ACCATGCCCACAAAGAAGAG GACCTGGCCTCACATTTCAC Repressed ACOT7 11332 GACCCTGTTGTGGACAGCTC TTCTTCTCGTCCTCGGTCTC Unresponsive gene with ARBR PYGO2 90780 GGCTCTTGGTCCTTGTTTCC GTGAGCAATCCAGGCTCTTC Unresponsive gene ADAM15 8751 CTCAGAAGCCACCAGAGCAC TCAGCCACAATCACCAACTC Unresponsive gene EFNA4 1945 CTACATCTCGGTGCCCACTC GGATCTTGGGAGGACTCTGG Induced EFNA3 1944 GCCTTGTGGCTCTGGTAATG ACGCTTCGATTTGCTCTCTC Induced SLC30A1 7779 TGGAAGAAGATAGGGCTGGAC CAGGGAAACATGGATTCACAC Induced PXDN 7837 ATGTCAGCCTTGCCTTGTTC AAAGGTTCTGTTCCGTTTGC Induced GLI2 2736 GTAAGCAGGAGGCTGAGGTG GGATGTGCTCGTTGTTGATG Unresponsive gene INPP1 3628 CAGAGGAAGAAACAGCAGAGC TGGGTCAGTAAAGGCAACATC Induced ARL8B 55207 GTTCCGTTCGCTCTTCTGG GAATTGACCTGACGCGATG Unresponsive gene BAP1 8314 ATAGGAAGCTGGCACCACTC AACGGGTTGTCTTGATCCTG Unresponsive gene TMCC1 23023 CTAGCCTGGGTGAGTGAAGC CCAAGGAATGGAAATTGGAG Unresponsive gene with ARBR SSR3 6747 CTCATCGCCCTCCTGTCTAC CTTGTGTCTCCCACCCTGAC Induced IL8 3576 GACAAGAGCCAGGAAGAAACC ACTGCACCTTCACACAGAGC Repressed TRIO 7204 ATATCCGCGAAGTCATCCAG TGTCCAGATCCTCTCCATCC Induced FAM105A 54491 CCCGTAACAAGCTGATGAGG ATGCCCTGGCTGAATATCTG Induced ANKH 56172 TCTGCATGGCTCTGTCACTC GTTCTGCAAAGGCAAAGTCC Unresponsive gene with ARBR LHFPL2 10184 GGCTGTTTCTGCTCCAACAC GTCTTGCTGTGCCCTTTAGC Unresponsive gene PHF15 23338 TTTGGACTGGACTGTTGCTG AGCTGCCTGAAGAAGATTGC Repressed FLJ36748 134265 GGAAGTAGCCCTCGTTCTCC ATCCCTCCATCCTCATTTCC Unresponsive gene with ARBR GRPEL2 134266 GCTTTGGCTCACTCTCACTTG AATACCCAACTGCCTGATTCC Unresponsive gene with ARBR GMDS 2762 CCTACCTGGCTGAGTTCCTG TGAGATCGCCATAGTGCAAC Unresponsive gene with ARBR

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HUGO Gene Symbol ENTREZ GeneID Forward Primer Reverse Primer Response to R1881 in HPr-1AR DSP 1832 TCAGGAGGGTGGAAGAAGAC TTTGGCAGCATCATCAAGAG Unresponsive gene with ARBR ITGB8 3696 AGAATCAAAGGCTGCAAACC CTTTCTGGACCCATCTGGAC Induced NOL6 65083 CTCCATGCTGGTTGTCTTCC GCAAAGAGGGATCTGAGCTG Unresponsive gene with ARBR ZFAND5 7763 CCCGTGAAACCAGTATTTGG AAGACCCTGTTGTTGGCTTG Induced C10orf104 119504 CAGAGAACCAGGAGGTTTGG ACAGGACAGACGCCATTCAG Unresponsive gene CAMK2G 818 CTGCAACACCACCACAGAAG CAGGCTCAAAGGAAGTGAGG Unresponsive gene FER1L3 26509 TAATGGCTGGGAAAGTGGAG GAGGTTTCTGGTCGATTTGG Unresponsive gene with ARBR KIAA1754 85450 AGTTCATGCCCTTCAACCTG CGCTCATAGACAGCAAAGGAC Unresponsive gene with ARBR BAG3 9531 ATGACCCATCGAGAAACTGC ACCTCTTTGCGGATCACTTG Unresponsive gene with ARBR EPS8L2 64787 CGGATGTCCACTTCTTCCAC CCGAATCTTCTCCTGGTGTC Repressed CCND1 595 GGAAGTGTTGAAGGGAGGTG AACGGTAGCAGCGCAATAAG Repressed BIRC2 329 CTGGGAACCAAAGGATGATG ATTCGAGCTGCATGTGTCTG Unresponsive gene FGD4 121512 TGGTGTGCAGCTTTCTTCAG ATAGCCCAGAAGTGGAATGG Induced KRT5 3852 TTCTTTGATGCGGAGCTGTC TCATACTGGGCCTTGACCTC Induced SPRYD3 84926 GTGATCCTGTCTCCGACTGC GCTCCGGCTCTATCTCTTCC Unresponsive gene with ARBR IGFBP6 3489 ACAGGATGTGAACCGCAGAG GGCCCATCTCAGTGTCTTG Unresponsive gene FBXO21 23014 ATAACGTGCTGGTGGAGGAC TGCGTTTGGGATGTAGTGAG Induced PLEKHG3 26030 GCATGAGCCACTCTTCATCC CCTTCACCAGCTCTTTCAGC Repressed GRAMD2 196996 GCTCCTTGAGTTGGGATGAC CAGGGATCATTGGTGGAGAC Induced BNC1 646 ACAGTGGAGGGCTGTAATGC AGGTAAGCTGCACGGAAATG Unresponsive gene with ARBR CDH3 1001 AAACCAGCACACCCTGTACG GCCTCATTCACATCCTCCAC Repressed OSGIN1 29948 ATGCAGAAGAAGCGAAGAGG CTACAGCACCGGACACAAAG Induced BCAS3 54828 AAGCAAGGAGGTCGCTGTAG CATCAAGCTGGGAAGAGGAG Unresponsive gene FAM104A 84923 CCCCTCTGTTCCCTCTCTTC GTCTTCTTCGTTGCCATTCC Induced CYGB 114757 CGTGGAGAACCTGCATGAC TCCAGAATGACCCCAGAGAG Unresponsive gene TBC1D16 125058 AGGTGGAGGAGGAGTACAAGC GTAATAGCGCAGCAGGAAGG Unresponsive gene with ARBR RAB11B 9230 GGTGTACGACATCGCCAAG CGCAGGTCACTCTTGTTGC Unresponsive gene with ARBR FLJ12886 56006 ATGTGTTGGTGGTTGGTGTC CCCTCGTTCCTTCATTTCAG Unresponsive gene with ARBR TMEPAI 56937 CAGCCATCTGGAGCAAAGAG CTAAGAAGCGCGGAGTGTTC Repressed COMT 1312 ACGCTTCTCTTGGAGGAATG CCAGGAACGATTGGTAGTGTG Unresponsive gene SFI1 9814 CGTCGCTGGAAAGAGAACAC TCTGCACTGACACAGCTTCC Induced PISD 23761 CAACCTCAGCGAGTTCTTCC CCTGCTCCACCTCACAGTTC Unresponsive gene TSC22D3 1831 CCCAGCTAGAGCGTGAGAAC AGCCACTTACACCGCAGAAC Induced PLAC1 10761 TCCATGAGAGTAGCCAGCAAG AAGACACAAGGTGGACAATCG Induced CETN2 1069 GTTGCCACAAGCAGTCATTC ACACATCCAAATGCCAGTGC Unresponsive gene ZBTB48 3104 GCTGTTTGTGTGTGAGGAGTG CAGGTGCATGTTGAGATTGG Unresponsive gene KLHL21 9903 GAACGAATGGGACAAGATCC CACGTCCGAGAGTTCAAATG Unresponsive gene with ARBR SOX13 9580 TCCTGGGACTGTAGCTCTCC GTCCAGCTTCTCCTGGCTTC Unresponsive gene with ARBR MCEE 84693 TCAAGCTCCCATTCCAACAG CTGCTATGGCTACATGGTTGAG Induced DPP4 1803 CCAAAGACTGTACGGGTTCC TTGCATTGGTGACTGAGCTG Induced LNX1 84708 TAAAGGTCAACGGGATGGAC ATCACAGTCAGCCACAGCAC Induced FGF18 8817 TGTGCTTCCAGGTACAGGTG GCTGCTTACGGCTCACATC Induced C6orf81 221481 TGGAGTGCAAACAGGATGAG GTAGCCCAGCAACACGATG Induced ZNF189 7743 TGACCCAGGAACAGAGAATG GTTGAATGAAATGGGCCTTG Induced TUBAL3 79861 GCTGACAAAGCCTACCATGAG AGCCGAGGATCACACTTGAC Unresponsive gene with ARBR SFMBT2 57713 AATCAACGCAGCCTACAAGC TATTTGGCCTTCAGCGTCTC Induced ANK3 288 TCTGCTGGAATATGGTGCTG TTCGCATTTCTACCGAGGAG Unresponsive gene with ARBR MMP7 4316 AACGCTGGACGGATGGTAG GATCTCCATTTCCATAGGTTGG Induced EPSTI1 94240 AAACCGCTGAGTTCTTGAGC TTCCATGTTGAGGATTGTGG Induced DNAJC15 29103 CTACGCATTTCGGATCTGG GACCAGCTTCTCGCCTACTC Induced SERPINB4 6318 AGTGAAGCCAACACCAAGTTC TGCTGATGTGATGCTGATAGG Induced ANGPTL4 51129 TGGCTCAGTGGACTTCAACC GTGATGCTATGCACCTTCTCC Repressed THBD 7056 GCTTGCTCATAGGCATCTCC CGCGCACTTGTACTCCATC Induced IL6 3569 TACATCCTCGACGGCATCTC CCATCTTTGGAAGGTTCAGG Repressed SOX4 6659 ACAGCGACAAGATCCCTTTC CGGACTTCACCTTCTTCCTG Unresponsive gene DST 667 TTCTGCTGCGTCACCTACC CTCCTGTGGCTGGAATAACC Unresponsive gene with ARBR KRT73 319101 ACAACAAGTTCGCCTCCTTC TGGGCTCCAGGTTATTCTTG Induced LAMB1 3912 GGCAATCCATCAGAAGTTGG CACCTCCCAGTCTCCTTGTC Unresponsive gene with ARBR TNFRSF1A 7132 GCCAGGAGAAACAGAACACC TCCTCAGTGCCCTTAACATTC Unresponsive gene with ARBR ALOX5AP 241 ACTTTCCTCGCTGTGCTCTG GTGCTCTGCGTTCTCTCTCC Induced PGS1 9489 TCACCAGGAGCAAGAGCAG TCTTCACCCACAGCTTCACC Unresponsive gene with ARBR TMEM23 259230 CCACACGGTCATGCTAACAC TGAGAAGCCAGCAAATCCAG Induced B3GNT5 84002 GGTCGTGTTCATCGTGGTG CGGCTGTGTAGTCAGGGTAAG Unresponsive gene with ARBR SEC14L2 23541 GGGAGATGACAGAGGTGCTG AAACCGCAGGACATAGATGC Induced SCAP 22937 AGGAGCTTGGAGGAGTTGTG AAGCGTTCCCAGTCATTCTG Unresponsive gene with ARBR NPAS2 4862 AAGGAGGTTTGCTTCATTGC TTGGAGGTGCTCTGTGATCC Unresponsive gene with ARBR PDE4C 5143 ATCATGGCCGAGTTCTTCC CACTGAGGCCGTATGCTTG Induced PITPNC1 26207 GTTGAGGGAAGGCTGGAGAG AGCAGAATGTCTCGGACCAC Unresponsive gene with ARBR AP3S1 1176 GATCAAGGCGATCCTAATCTTC CTCCCTGATGATTTGCTGTTG Induced

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HUGO Gene Symbol ENTREZ GeneID Forward Primer Reverse Primer Response to R1881 in HPr-1AR PIK3R2 5296 ACTCACCTTCTGCTCCGTTG TTGACAATCTGGTCCTGCTG Unresponsive gene with ARBR DLGAP4 22839 ACTCGGATACCCAGGATGC TCGATGCTGATGGAGTTGG Unresponsive gene with ARBR ERN1 2081 TCCCTCAACATCGTTCACAG TTCTTGCAGAGGCCAAAGTC Induced TNS4 84951 GAGAGAACTGGGAGGTGCAG AGCTCAGGTACAGGGTGTGG Repressed TULP4 56995 ATTCAGTACGAGGGCAGGTG TGACAGACCCAACCAGGAC Unresponsive gene with ARBR LTBR 4055 AGAACCAAGGTCTGGTGGAG TGGCAAGGAGCAGAAAGAAG Unresponsive gene with ARBR TNFAIP3 7128 GCACGCTCAAGGAAACAGAC TGTCCCATTCATCATTCCAG Unresponsive gene with ARBR UFD1L 7353 GAACTGCGTGTGATGGAGAC CATGCTGGACTTGTCTTTCG Induced DNER 92737 CAGCTTGTTGCAGATCCTTG AAATGCAGAGGTAGCCATCG Induced NDRG1 10397 ATTATTGGCATGGGAACAGG CAAGGGTTCACGTTGATAAGG Induced DYRK1A 1859 TGCAAACCTTCATCTGTTCG AAGGCAGAAACCTGTTGGTC Induced C1QBP 708 TTGGGAGCTGGAACTGAATG ATCAAATGTTGGTGGGATGC Unresponsive gene with ARBR TNFAIP8 25816 CGTGGTCAGTTTCCATCAGG TGTGACTTGGCAGTGAGGTG Unresponsive gene with ARBR DPF2 5977 AAAGGGTCCTGATGGATTGG AATTGGAGGCAAGATGGATG Unresponsive gene with ARBR RHOU 58480 CCGGACAGGATGAATTTGAC GACGTTCTGGAAGGATGAGG Induced SERTAD2 9792 TCGAGGACGACGATGACAC CCAAGGCAGAGGAGAAACTG Unresponsive gene with ARBR JMJD1A 55818 CAGGGTTGCTCTCAAAGTCC TTAGGAAGGCCAGTCAATGC Unresponsive gene HYAL1 3373 GCACAGGGAAGTCACAGATG GCAGAAAGTGGTTTGTCGTG Unresponsive gene NAT6 24142 CTACACACCGGATGGAGCTG TCATCTCTGGTTGGCATGTG Repressed HYAL3 8372 AACCAACTCGGCCTCTATCC GCTGTGGTGGATCTGGTAGG Unresponsive gene PHF7 51533 GGTGGTGCCTCATTCTGTG CACTCCTCACACTCCCATTTC Induced WWTR1 25937 CAGCAATGTGGATGAGATGG TCAAGGAAATCAGGGAAACG Unresponsive gene LPP 4026 TGGACGCTGAGATTGACTCC AACTGGAGGAGAGGCTGTTG Induced CD38 952 ACTGCCAAAGTGTATGGGATG GCAAGGTACGGTCTGAGTTCC Unresponsive gene MTHFD2L 441024 CACTACCAGACCACGTTGATG GGCAGGTATGAGAGAATGCTG Unresponsive gene with ARBR EPGN 255324 TGACAGCACTGACCGAAGAG CCAGGCAAAGGTGTGAGAAC Repressed TLR2 7097 TGGAAGCTGGTGGCAATAAC GGGATGGAGAGTCACACAGG Induced SLC26A2 1836 GCAATTATGGTTGGCAGCAC AATCCACTCAGCAAGGCATC Induced LEMD2 221496 TGGTTGAAAGGAGAAGACCAG GATGAGCACGTTGGTGACAG Unresponsive gene with ARBR DEF6 50619 CTGGTGCCTCTTCAACTTCC CACCTCCAAGCTCATGCTG Repressed PPARD 5467 TGATGCCCAGTACCTCTTCC TCTCGGTTTCGGTCTTCTTG Unresponsive gene TBC1D22B 55633 TCCCTGCCAACTACAAGGTC GGAGTGATTGCTGTTTGTGG Induced RNF8 9025 AGCATCTTCAGGGTTTGGAG CCTTCTTGCTGCGATTTAGC Unresponsive gene with ARBR TJAP1 93643 TGCCCGAGTGTTAGAGAAGC CCACATGCACAAAGACATCC Induced VEGFA 7422 CCTTGCTGCTCTACCTCCAC GAAGATGTCCACCAGGGTCTC Induced UST 10090 ACTATCCCGAGTGCTCCAAC TCATTCACGTTCAGCTTTGC Induced PBXIP1 57326 CTCTTCTCAGGTGGCCTCTC AGCTGTTCCCTTAGCCCATC Induced FLAD1 80308 CTTCACCCATGTCCTCACAG ATAGCTTCTCCCAGCCTTCC Unresponsive gene LENEP 55891 CCAAACCCTACCCTTCTTCC CCAGCAGTTCCTTGATACACC Unresponsive gene ZBTB7B 51043 ACCTCAAAGGCCAGAACTGC AGAGAGAGGCGGAAGGTGTC Induced DCST2 127579 TTATCCGACACCTCCTCCTC CCAGCGTAGCCAGTACCTTC Induced RAG1AP1 55974 GCAGTGTCTTCACCATCAGC GAAACCCATAGAGGCACCAG Induced DPM3 54344 ACTGTGGGCTATCGTGTGG AATGGGAGGAAGGGCTGTC Unresponsive gene C1ORF2 10712 TGCAGCTCAGAAACAGATGC CTCCTCGTAGTCCCATGACTG Unresponsive gene SCAMP3 10067 CCAGGATGTGCTCTTTGTCC CACGGATACTGCTGTGTTGC Unresponsive gene CKS1B 1163 CGGACAAATACGACGACGAG GCCAAGATTCCTCCATTCAG Unresponsive gene SHC1 6464 AGGAGGAAGAGCCACCTGAC TCCCGAAGCCTCATGTCTAC Induced CXCL3 2921 ACCGAAGTCATAGCCACACTC CCCCTTGTTCAGTATCTTTTCG Repressed EREG 2069 CATCTTCTACAGGCAGTCCTC CCATTCATGTCAGAGCTACAC Repressed SERPINB3 6317 CGCGGTCTCGTGCTATCTG GTAGGTGATGATCCGAATCC Induced GBA 2629 CAGCCTCACAGGATTGCTTC TACCAAGGGCAGGAAAGGTC Induced PDE6A 5145 TGACTTTGTTTGCACCTTCG TCTTCTCCTCCTGCACCTTC Induced WDR46 9277 AGTTCCTGCCCTTCCACTTC CATTCAGAGCTGCCACAATC Unresponsive gene with ARBR PKHD1 5314 GGCCTGAGAGGACAGAACAC TATTTCCAGGGCAACAGAGC Unresponsive gene with ARBR AKR1D1 6718 AGAGATGAGAATGGCAAATGG CCTGGCTTGTTCAGGATGAG Induced MGAM 8972 TACCAATCCCAACTGTGCTG GAACATCCTGAGACCGAACC Unresponsive gene with ARBR LRRC8A 56262 TCTTCTACGGCCTCATCTGC AAGGCGAAGTCGTTCTTGAC Induced HKDC1 80201 CCTTTGGGCTTCACATTCTC TTCTCCTCTTGATGGCTTCC Unresponsive gene with ARBR DCLRE1A 9937 GTTCTCTTCTTGCGGACCAG AGGCAGTGTTGATGGCAAAC Induced SCNN1A 6337 TCTGCACCCTCAATCCCTAC ACAGGTCAAAGAGCGTCTGC Unresponsive gene with ARBR SOAT2 8435 GGACCATGCTGTTTCTAGGC GTATGGCAGGACCAAGATCG Induced NAP1L1 4673 GTGAAGAAGCGGATGAGGAAG CACTCTGCTGGGTTTTGATCC Unresponsive gene NTN4 59277 ATTTGGCCTGGAAGATGATG TCGTATGGTGGTGACAAAGC Unresponsive gene with ARBR NFYB 4801 AGGTGCCATCAAGAGAAACG GTGACTGCTCCACCAATTCC Unresponsive gene DAAM1 23002 CTTACCCGCATTTCATGTCC GGGTCCTGTCCTTTGTCATTC Unresponsive gene with ARBR CRISPLD2 83716 GGGAACTGGATTGGAGAAGC CCGTTTCCACCTCATTCATC Induced DCST1 149095 GCAACTTTGGGCAGACCTAC CTCCCAGCTTGTGTTGAGC Induced KRTCAP2 200185 CTTTGCTGGGATGCAGATG AGCGAGAACACGAAGAGACC Unresponsive gene TRIM46 80128 ACCTGTCCTGCACTTCTTCC CCTGGAACACTCCGTACTGC Unresponsive gene

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HUGO Gene Symbol ENTREZ GeneID Forward Primer Reverse Primer Response to R1881 in HPr-1AR MUC1 4582 CTGGTCTGTGTTCTGGTTGC GGGTACTCGCTCATAGGATGG Induced THBS3 7059 AGGACACCAAGGACAACTGC GGACCAGGAGGCACATAATC Induced CREB3L2 64764 GTGTCAATGGAGGTGGAACC GGTGGTAATGTGGGTGAAGG Induced THOC3 84321 GCAACAAGGATGATGTGGTG CAACCATTGCCATTTGTCAG Unresponsive gene ANXA8 244 GCTCATTGTGGCCCTTATGT AGGCCAGGATCTCAATGATG Repressed ASB9 140462 CACCTGGGCACTCCACTCTA ACCAGCTCCACAGGACGTTT Induced ARHGAP26 23092 GTGGTGTTTGGACCCACTCT TATCGGGCACGGTGTTAAAT Induced F3 2152 CCGACGAGATTGTGAAGGAT CCGAGGTTTGTCTCCAGGTA Induced GPR153 387509 CCTTGGAGTTCCTGCTGTGT AGGTGGACACGAAGACCTTG Induced IGFBP1 3484 TCACAGCAGACAGTGTGAGAC AGACCCAGGGATCCTCTTC Induced SLC9A2 6549 TGATGATAAATATCTGCGGAAGC TTCACGACAATCATTTAGAGATGC Induced IRS2 8660 GGCTTCGTGAAGCTCAACTG AGAAGAAGCTGTCCGAGTGG Induced CPEB4 80315 GTCAGCAACAGGAACAGCAA GACGATGCGCTAGATGTCAA Induced ATP1A1 476 AGACCGAATTCCTGCTGACC AGAAGGCAATGTTCCTCGTCTC Induced RAB11FIP1 80223 CAAGGAGCGAGGAGAAATTG GGTGTCTGACCCACTGTCCT Induced SDPR 8436 CAGCGTGTTTGTGAAACAGC GGGCAAATCATCATCTGAGG Induced SLC19A2 10560 TTTGGGTGTGCTATGCATCC GCCACTGGCATCTACCACAA Induced PYGB 5834 CTGCTTCAAGGACATCGTGA TGACCTTCTTGGTCCACTCC Induced BRF2 55290 CAGAAGTGGAGACCCGAGAG GACAGTGGAGACAGGGGGTA Induced STOM 2040 CAGACACTGACCACCATTGC TTCATGCTTGGAAGGCTAGC Induced MT1X 4501 AAGAGTGCAAATGCACCTCC ACAGCAGCTGCACTTGTCTG Induced AMIGO2 347902 CATGCCCCTGCAAGTGTAAA TCAGGGGTTCCAAAAACACC Repressed VIPR1 7433 ATTCAAGGCCGCAATGTAAG AAACTCGCTGCCTTGTCATC Repressed CXCL2 2920 GCAGGGAATTCACCTCAAGA GACAAGCTTTCTGCCCATTC Repressed SEC22C 9117 TGCTCCTAATTTCCGAATGG AAATGCAGGCTACGAAAGGA Repressed ANKRD1 27063 TTAGCGCCCGAGATAAGTTG CACAGGCGATAAGATGCTCC Repressed GPR115 221393 AAGCTTGGTTCTTTGCCTGA AAACCACACATTGGCAGTCA Repressed AIM1 202 TCCTTTCATCCTGGAACCTG GGCAAATGATCGTCTCCAGT Repressed CYR61 3491 GTGGAGTTGACGAGAAACAATG CTGGGACCATGAAGTTGTTTG Repressed CYP4B1 1580 GGCTTTCTCAAGCTCATCCAC GCCCAGGACACCACTTTG Unresponsive gene with ARBR DHCR24 1718 TGTTGCCTGAGCTTGATGAC GACCAGGGTACGGCATAGAA Unresponsive gene with ARBR PDE4DIP 9659 TCCGGGATGTTGGTATGAAT TTATTGGCAAAGGAGCCATC Unresponsive gene with ARBR EFNA1 1942 TACCTGGTGGAGCATGAGGA AACCTCAAGCAGCGGTCTTC Unresponsive gene with ARBR CDC42EP3 10602 TCTGTGTTCACAGAAACGCC CATGAGAGCTTGGGATCCTC Unresponsive gene with ARBR NET1 10276 GACCTGCAGGATGGAGATGT CTTGTGGAACACGTCATTGG Unresponsive gene with ARBR ASB13 79754 CATGAGACTGCCCTTCACCA CCAGTGGCCTTCCTCAAGTT Unresponsive gene with ARBR DEAF1 10522 TGTTTGAGCAAGCCAAGCAT GCTGGTGATCCTTCCAGTCC Unresponsive gene with ARBR BIRC3 330 GACAGGAGTTCATCCGTCAAG TTCCACGGCAGCATTAATC Unresponsive gene with ARBR VGCNL1 259232 ATGTGAAAGATCGCTGGTGTG ATAATCAGTGGCCGTGGAATC Unresponsive gene with ARBR ABHD2 11057 ATGAATGCCATGCTGGAGAC TCAGGTTCAAACACCGGAC Unresponsive gene with ARBR CDH1 999 TGGAGAGACACTGCCAACTG TTAGGGCTGTGTACGTGCTG Unresponsive gene with ARBR ENTPD6 955 AACAGGACATTCCGTTCGAC TTCCGTTCATGATGGAAACA Unresponsive gene with ARBR ID3 3399 AATCCTACAGCGCGTCATC GGCTGTCTGGATGGGAAG Unresponsive gene JUN 3725 GCTCGGGCTGGATAAGGGCTCA GATTTGCAGTTCGGACTATACTG Unresponsive gene LAD1 3898 AGATACCACACGGCCATACG TGAGCCTTGATGTCACAACC Unresponsive gene BHLHB2 8553 TGAAGGCCATTTCACTAGCAG GTAGAAGGGCAGGCAGAAAG Unresponsive gene CNO 55330 AAGAAGCTCCTGCACACGAT CAGAGCTGAGGCCTTTCACT Unresponsive gene KRT6A 3853 TGCTGCCTACATGAACAAGG TGTCTGAGATGTGGGTCTGC Unresponsive gene MT2A 4502 GCAAATGCAAAGAGTGCAAA ATCCAGGTTTGTGGAAGTCG Unresponsive gene MLYCD 23417 AAACTGGATGGACATGAAGC ACGATTGCCTGGATGTTG Unresponsive gene MTP18 51537 TCTAGCCTCTGTGGCCATTC TTCCCCACTGTTGGGTAGAG Unresponsive gene

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Supplemental Table 4. Real-time quantitative PCR (qPCR) primers for AR binding region (ARBR) validation DESCRIPTION/ARBR FORWARD PRIMER REVERSE PRIMER Control, NO_ARBR_HSPA1A promoter TCTGGAGAGTTCTGAGCAGG CCCTTCTGAGCCAATCACCG ARBR2.16 ACAGGTAGGGCTGGAGAAGG AAAAAGGAGGAGCACCACAG ARBR2.17 GACAGCTCCCGAATCATCAG GTTGCCAGGGTTGTACCAAG NO_ARBR_SGK (+471 from +1) TGCCAGCGGTAAACATTCTC CCAGTTCAAGCCAAATCAGC NO_ARBR_SGK (-282 from +1) GCGGCGGAATAAATGAGAG AGGGCCGTTATCAGTCTCC ARBR6.35 AGGGTTTTCAGGTGGGACAG TGAGGAGGTAACAAGCGAAGG NO_ARBR_SGK (-1924 from +1) TTCCCTTCTCTCGGTTTGG GCCTTTTCCTTGGTCTTGG NO_ARBR_SGK (-2576 from +1) GTGCAGGTTGATGTTTCTGG GTGACTTTGTTATTGCCAGTGC NO_ARBR_SGK (-3049 from +1) GCAATGGGGAGAATAAATGG AGACGGCTATCCCTGTTCTG NO_ARBR_SGK (-3667 from +1) ACCAGGGAGTATGAGGAAAGG TTAACACTGCACAGGCATTAGG NO_ARBR_SGK (-899 from +1) CCTTCCTCCTCTTCCAAGTTC AAGATTTCCTGCCCCGAGTC NO_ARBR_SGK (-1482 from +1) CCTCTCTTCCCTGCCTTCTG ACCTCGCTCGCTCTTTATGTG NO_ARBR_TIPARP (-3152 from +1) TTAGACAGGGTCCTGTTCTG ACGGTGGCATGCATCTCTAG NO_ARBR_TIPARP (-2993 from +1) CGTAGAGATAGGGGTCTCAC GTCTCATTTTGGCCACGCAG NO_ARBR_TIPARP (-2581 from +1) AAGTCTAGAGGCAGCCAGTC GATGGAAGCAACAAGCTAAGG NO_ARBR_TIPARP (-2065 from +1) GAGGCTGAGAAACTAGCCAG GGTATAGCCCAGTTCCAAC NO_ARBR_TIPARP (-1734 from +1) CTTGCACATTGAGGCTTGTC CCACGAGCTAAGGATGCTG NO_ARBR_TIPARP (-1128 from +1) CACTGACCAAGATCTTGTCTC CAGGGCCATTAAACTAAGGTG ARBR3.30 ACAAGGCCCACGAAATAGTC CACCCTGTGAGGAAGCAAAC NO_ARBR_TIPARP (+503 from +1) GGCAGGTGTATACATCAGACC TCCTAGGCGCCTCAGAGCAC NO_ARBR_SGK (+1346 from +1) TTCTAGCCAAGTCCTTCTCAGC AAACTGCCCTTTCCGATCAC ARBR6.34 TTGGCGGTAGACACTCCTTG GGGTGCTTCACATTCTTCAAC NO_ARBR_SGK (+2201 from +1) GGCTCGTTTCTATGCTGCTG ACAGCCAGTGCTACGTCTCC NO_ARBR_SGK (+2659 from +1) TCGGACTCTGCAAGGAGAAC GGGTAAACCAGGCACCAAAC NO_ARBR_SGK (+3223 from +1) AGGACTGTGGACTGGTGGTG GTAGGGAGCAGGCAGTGTTC NO_ARBR_SGK (-8870 from +1) CCATGCCAGGAGAGTAGTTCTG AAGTGAGGAATGTGCTGGAAAG ARBR2.15 GTCATCAGCCCAGTCATGC GGATCAAAGTGCCCAAGAAG ARBR3.31 CGGTTTGGTATGGTGGAGAG CACGAAGAAGGAGGGATCTG NO_ARBR_TIPARP (+2024 from +1) GCTGTGTGCATTGTGGTAGC ATTGTGCCAGGTGAGAAAGG ARBR3.22 TCCAGCCCCATAACTCCTAC ACTGTTCTGTCCCCTCATCAC ARBR3.23 CCCTCTTCTGTGCTACTCTGG ACGGTGTGTTTCTGAGAGAGTG ARBR3.24 AGCGCATCTGAAATGTTACACC GCTGACCCTAGAAGGGATTATG ARBR3.25 ACACACTCGTGCTGGACAAC TCCTGCCAACTGAACTACCAG ARBR3.26 AAACAGTCCAACTGGCAAGG CGGAACAAGATGAGAATGGTC ARBR3.27 GGCCTGCTCTAGGGTCTTATG CAAACCACAAGGGAATGAAAG ARBR3.28 TGAGCAAAGGCAACTTGAGTG GGAATCCTGCAAAGAGACAGG ARBR3.29 AGGCTTTCCCAAGTGATTCTG AGCGGTAGTTATGCAATGGTG ARBR1.15 TTATCTTCAAGCTGCCTCACC GACTGGCTGAACCTCTTAGGC NO_ARBR_SSX2IP TGCACATTTGGATCTCATGTC CAAACTGCCACATGCTTAGTTG ARBR1.23 TGCCCTCCATTAGGTATTGC AATCTCCTCTTCCTGCTGTCC ARBR1.24 GCCAGCCAAAGCTAGTCATC AGGCTACGGCAAGTCAAGG ARBR1.52 TCCCGTGGTTAAACTTGGTC TGTGGCTTCTGTAGGTTCTGC NO_ARBR_SLC30A1 TGAGGCTCTATCTGGGAAGC TAAAGCAGGACCAGCCAAAC NO_ARBR_SLC30A1 CCAGTGCTAGGAGAAGGAGAAC CTTTATCTGGTGGAGCGACATC NO_ARBR_MPHOSPH10 GAGAAGAGATGGGACAAGATGC TGTCGAGGTTGAGTTGGTTTC ARBR2.10 TTCCCAACAGAAAGCTGGTC TACCGCGCACCAATAAAGAG ARBR2.31 CCAAAGGCTGGAGAGAGATAAG GATGTTCCTCAAGACACAGCAG FALSE_NEGATIVE_ARBR_INPP1 AATCTTCCCAGAGCAGGAGAG TGTTGCTGTCATTACCTCATGG ARBR2.39 AACGGATGGAAGCGATACAC TTTGCAGACACCAGCAGAAG ARBR2.40 TCATTCCCTGATGTCTGTGC GAGAAAGTGAGTGGTGGATGG ARBR2.41 TGCTCTCACAGAACAAACAGG TTGAGTTACCCAGGCTTTCAC ARBR3.09 CCTGTGGGAATAGCAAGGTC AACCCAGGAGTTGCAGAAGC ARBR3.10 AGGACAGAGGGTGACAGTGC CCTGATTCGGTGACCTGTG FALSE_NEGATIVE_ARBR_OSBPL11 TTCCATTCAGCATCCAAAGAG ACTGGTAGGGAAGGCACAGAG ARBR3.12 GCAGCCTACGAAAGTCCATC ACCCAGAGTTGGAACACAAAG ARBR5.01 TGTGGTGGGAGAGACAACAG ATTTCAGCAGGCGAAGTAGC

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DESCRIPTION/ARBR FORWARD PRIMER REVERSE PRIMER ARBR5.14 CCCTTGGAGTTAGCCACAAC AATGGAGCAGTGTGCATGAG ARBR5.15 GGGAAGAACAGCTTGCTCAC TGCCTCACCCTAGTCAAAGC ARBR5.33 CCGAAGCTGAAGGGAACAC GCCAGGTCGTCCAGTTTATC ARBR6.29 CAAGCATAAGACAGGCAGAAAC CCAGAGAGAACAGTGCAGAATG ARBR6.30 ACCCTCCCAGGAAGAATTATG CCTTAGATGAGCGGTAGAGAGG ARBR6.31 AACTGCCCAGGACACCAAG CCAACTCCAGCATTGTAACG ARBR1.12 TCCACTTCCAGAATGTCCATC AGGAGCAGGGTAGCAAGACC ARBR1.49 CCGTGTTTGTGTCCTTCAGC GACCCATTGCTTCACTTTCC ARBR2.04 ACTGTCACTCAACGCCCATC CAGCTTGGACCTCAGGAAAC ARBR2.07 ATCTGTCCCACAGCAAACACTC GGGACCAAGTGTCTCTTCACTC ARBR2.23 GCACAGTCAAGAGAGGCATTAC TGGTCTCTCAACCTATTGATGG ARBR2.24 CTAGTGGTCCTTGGCTGGTG ATCCTCAGATGCTGGCTTTG ARBR2.25 TCCTTGAAGTTCCCTTGATCTC ATACATGCCAACACCACTGAAG ARBR4.08 GGTGACAAATGGTCCAATCC GTGTCTCATGCCTGTTCAGC ARBR4.09 ATAAGACTGCGATGCCTTGG ATCTGTCCCTGCCAACAGAG ARBR4.10 GCCACACACAGTCAAAGTCG GGAGTTGCTGGTGATCTAGGC ARBR4.01 TTGGGTATTCAGAGGCATCC CCAGGACTGTGGGAATGAAG ARBR4.05 CCATACCCTTTCCATTCTCG CTTCTGAGTGCTTGTTGTGG ARBR3.20 ATTTCTGAGCCGCCACTTC CAGCCAGTCTCCAAGGATTAG FALSE_NEGATIVE_ARBR_MME TTAAACTGCTCGGCCAATATG CCCAGAAAGGACAAAGTGAGG FALSE_NEGATIVE_ARBR_MME TGGGTGTTGCTAGTGTTTGTG TGATGCAGAACAGCAAGAGAG FALSE_NEGATIVE_ARBR_SLCO2A1 ACTTCCACCACACCAAGCTG AGACAGCCAGGAAGGCATAG FALSE_NEGATIVE_ARBR_SLCO2A1 GCAGCCAGTGAGGTGAAGAG CAAGTTCCCAGGTCAGGAAG ARBR3.16 CTCCTGAAACTCTGGCAACAC CTGGAAACCCAATCATTTCTG FALSE_NEGATIVE_ARBR_AREG CTGTATTGTATGCCGTGGTG GCAGCTCCTTTAGGCCAAG ARBR4.14 GCAACACAAGGAACAAGCAG ACAAGGTGCTGGGAGATAGG ARBR4.15 CCCAGCGCAATAACAGATTAC TTGTCCAGCCTCAGAAAGAAC ARBR4.16 GCATTTCCAAGCCTGTTTAGC AGTCTGCATCCACCAGGAAG ARBR5.16 CAAGTGACGCCATCCAGTC CAGGAACGCAAGATTCACAG ARBR6.33 TCCCACGAAGTGCTTGTCTAC GGCAGGGTTCTGTGTTTCTTC ARBR8.04 ATCTTCTGGCTCTTGGATCG GCAGCACTAAAGGGCATCTC ARBR9.04 CCTGCCAAACGAACTGAAC CTGGTAGCCTCTCTGCTTCC ARBR10.04 TCCACCTACCTCGGGTTTC GCCTGCACTTTCCTGATCC ARBR10.05 ACTGTGTGAGGTCAGCAACG CCACTCTGCACGGAAACAC ARBR10.06 GCTCAGGCTCACTCTGTTCC CCCCATCTCTACCCATTCTG ARBR12.09 CCTCTTTCACAACCATGTGC GACAGAAACGCAGGAACCAG ARBR4.17 GCAGCAAGCCAGAGGATTAG CTGTTCCTGGTCCTGACACC ARBR4.18 TCCTAACCAAGTGCGTGAGC CTAGACTGACGGGTGGAAGG ARBR4.19 TTCTGAGCACGGGTACATTTC TTGGAGCAACTTCATTTCAGC ARBR1.25 GAGCCTGCAACTCATTACTGC TGCATCTGACCACTCTCCTG ARBR1.26 GGGAACAAGAGGACATGCTG GCCTCATTCTCACCCTTGAC ARBR1.27 CTGGCAAAGGTCCAGACAC GCAACAGCTCCAAGAAGTGC ARBR1.28 GAGTTTCCTGTCACTGCTCTCC CTAAGGGCACAAGGTCAAGC ARBR1.29 CTGCGAGTGCTGTAGGTGTC GGAAACAGGTGCTCATGCTC ARBR1.30 GGGCTTAGAAAGGATGAGGTC CCCTTCCCATTAGCAGTTCC ARBR1.31 GATGTGTGTGCTTGGGTGTC CCAGGGATTCTCACTCCTACTC ARBR1.32 GAGCGGTCAGATGGAAAGC AGTGCGGGCAGTAAATATCC ARBR1.33 GGTGGAGCATGAGGAGTACC CAGGGTGAAAGGTGTGAAGC ARBR1.34 TTAGGTGGTGGGAAGAATGC TGCAGTGAGCTATGATTGTGC ARBR1.35 AATGTTTCGTTCTGGCCTTG GCTTGTAAGAGCAACGTGGTG ARBR1.36 GACCTTGCACACAGGCTTC CCGAGTGACAGAGTGACATCC ARBR1.37 AGGCTGGGTTGTTATGATGC CCAAGGAAGACAGGGAGGTG ARBR4.13 TGTGATGACTCAGGTTTGC TGTGCCTTATGGAGTGCTCC ARBR1.41 CCGGAATGTCCATTCAGTTT TCCTGGGCTTCTGATGTCTT ARBR1.48 AGTGAATGGGATTTGGCAGT AAGGGGTAGAGCAGAGCACA ARBR2.32 ACCCAGTGGGAGGAGAAGTT GGGGAACAGGAAAGAAAAGC ARBR2.33 GCCACATATTTGTGCGAGAA AGTTCAAAAGCAGGGCAAGA ARBR4.29 AGCTGATGTTCAGCACAGGA CCTGGTGTGGTCTCTTGCTT

25 Bolton_et_al._Supplement

SUPPLEMENTAL REFERENCES

Baugh, L.R., Hill, A.A., Brown, E.L., and Hunter, C.P. 2001. Quantitative analysis of mRNA amplification by in vitro transcription. Nucleic Acids Res 29(5): E29. Ben-Dor, A., Shamir, R., and Yakhini, Z. 1999. Clustering gene expression patterns. J Comput Biol 6(3-4): 281-297. Bohlander, S.K., Espinosa, R., 3rd, Le Beau, M.M., Rowley, J.D., and Diaz, M.O. 1992. A method for the rapid sequence-independent amplification of microdissected chromosomal material. Genomics 13(4): 1322-1324. Cleutjens, K.B., van der Korput, H.A., van Eekelen, C.C., van Rooij, H.C., Faber, P.W., and Trapman, J. 1997. An androgen response element in a far upstream enhancer region is essential for high, androgen-regulated activity of the prostate-specific antigen promoter. Mol Endocrinol 11(2): 148-161. DePrimo, S.E., Diehn, M., Nelson, J.B., Reiter, R.E., Matese, J., Fero, M., Tibshirani, R., Brown, P.O., and Brooks, J.D. 2002. Transcriptional programs activated by exposure of human prostate cancer cells to androgen. Genome Biol 3(7): RESEARCH0032. Fox, M.S., Ares, V.X., Turek, P.J., Haqq, C., and Reijo Pera, R.A. 2003. Feasibility of global gene expression analysis in testicular biopsies from infertile men. Mol Reprod Dev 66(4): 403-421. Hughes, T.R., Mao, M., Jones, A.R., Burchard, J., Marton, M.J., Shannon, K.W., Lefkowitz, S.M., Ziman, M., Schelter, J.M., Meyer, M.R., Kobayashi, S., Davis, C., Dai, H., He, Y.D., Stephaniants, S.B., Cavet, G., Walker, W.L., West, A., Coffey, E., Shoemaker, D.D., Stoughton, R., Blanchard, A.P., Friend, S.H., and Linsley, P.S. 2001. Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer. Nat Biotechnol 19(4): 342-347. Li, H., Rhodius, V., Gross, C., and Siggia, E.D. 2002. Identification of the binding sites of regulatory proteins in bacterial genomes. Proc Natl Acad Sci U S A 99(18): 11772-11777. Nelson, P.S., Clegg, N., Arnold, H., Ferguson, C., Bonham, M., White, J., Hood, L., and Lin, B. 2002. The program of androgen-responsive genes in neoplastic prostate epithelium. Proc Natl Acad Sci U S A 99(18): 11890-11895. Patil, C.K., Li, H., and Walter, P. 2004. Gcn4p and novel upstream activating sequences regulate targets of the unfolded protein response. PLoS Biol 2(8): E246. Tusher, V.G., Tibshirani, R., and Chu, G. 2001. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 98(9): 5116-5121. Zaret, K.S. and Yamamoto, K.R. 1984. Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element. Cell 38(1): 29-38.

26 Bolton_et_al._Supplement

SUPPLEMENTAL FIGURE LEGENDS

Supplemental Figure 1. The 157 putative androgen-responsive genes (ARGs) identified by expression microarray analysis. The colorimetric representation shows GenBank accession numbers corresponding to genes, indicated by HUGO Gene Nomenclature Committee gene symbols, whose transcripts were repressed (A, green) and induced (B, red) by androgen. The color intensity reflects the relative fold change in transcript level for androgen- versus vehicle- treated cells. The time course spanned 4, 8, 15, and 24 hours.

Supplemental Figure 2. DNase I hypersensitive site (DHS) mapping revealed an androgen- dependent hypersensitive site at the ARE upstream of SGK. Androgen increased DNAse I accessibility at two DNase I hypersensitive sites (black triangles). Cleavage of the 5.5 kb parental Xba I fragment (-4,579 to +946) was androgen-stimulated at the ARBS (-1174 to -1160) of the ARE resulting in a 2.1 kb fragment (DHS1); an additional androgen-independent 1.0 kb fragment (DHS2) was also generated by DNase I cleavage at the transcription start site (+1) of

SGK.

Supplemental Figure 3. Distribution analysis of androgen response elements (AREs) located near

ARGs. (A) The distribution of AREs identified by ChIP-chip was plotted relative to the predicted transcription start site (+1) of the shortest transcriptional variant of the nearest ARG.

AREs reside great distances upstream and downstream as well as near the promoter. Notably, fewer AREs were found upstream than downstream of ARG transcription start sites of the shortest transcriptional variants. Relative distances upstream (negative) and downstream

(positive) of the transcription start sites (vertical black line) were assigned to 10 kb bins. AREs

27 Bolton_et_al._Supplement were generally found beyond 10 kb of the transcription start site (B) The location of AREs is shown relative to the predicted gene substructure of the shortest transcriptional variant of the nearby ARGs. When the distribution of all AREs near all ARGs was assessed, most AREs were situated downstream of the transcription start site. These distributions were subdivided based on whether the ARG was repressed or induced, suggesting biases in terms of ARE location and the mean AREs/ARGs ratios.

Supplemental Figure 4. The number of AREs containing putative ARBSs. All 524 ARE sequences were scored for putative ARBSs using a predicted position weight matrix (PWM) representative of the ARBS (Figure 7A). The percent of ARBRs predicted to contain ARBSs

(red squares) with varying score cutoffs was plotted. The false positive rate (blue triangles) was calculated by randomly sampling unbound sequences at varying score cutoffs.

28 Bolton_et_al._Supplemental_Figure1 A 4hr 8hr 15hr 24hr B 4hr 8hr 15hr 24hr FST AA701860 SEMA3G AA732915 DKK1 AA253464 TMEM37 N93191 ARL4C N35301 S100P R32952 DDIT4 AA447746 AQP3 R91904 CYP24A1 N21576 CXCR7 N53172 ADAMTS1 R76553 KRT73 W74418 FGFBP1 AA936757 SLCO2A1 AA037014 KCNN4 AA443903 MGC16121 R32951 PLK2 AA460152 TIPARP AA707871 CXCL1 W46900 SGK AA486082 PHLDA1 H26271 RIPK4 W72972 GPRC5A AA172400 ACSL1 T73556 AREG AA857163 KLF4 H45711 MYC W87741 LNX1 T84156 EDG2 AA193405 EPB41L4B H94262 CD274 R78533 SERPINB3 AA398883 BMP2 AA011062 ACSS1 N67766 PLAU AA284668 PAG1 N50114 NT5E R60343 PRSS23 R76394 SNAI2 H57309 C17orf80 AA400592 IL6R T52330 SPTLC3 AA010557 ANTXR2 T59658 HMGB3 AA056377 PTHLH AA845432 FOXO1A AA448277 FAM84B N66178 FKBP5 W86653 INHBA R66924 SLC22A3 AA460012 ZMIZ1 AA443116 ST5 AA446290 PHF15 AA454791 NEDD4 AA442095 TM4SF1 AA487893 PXDN W72043 IRF2BP2 AA598781 FBXO21 R39464 PLEC1 AA448400 CREB3L2 R34297 DCBLD2 AA431438 SLC30A1 R31168 TP73L AA455929 NFKBIA W55872 DUSP5 W65461 SLC12A7 AA427732 ANXA8 W81668 KIAA1727 H56655 ARID5B W93382 ITGB8 R74357 KIAA1434 H91615 INPP1 H52141 ELK3 H97146 TFPI2 AA399473 DNMBP AA453501 FOXC1 AA495846 PNKD R01094 KLHDC8B T70612 UAP1 N68465 KIAA0232 AA406589 SEMA4B AA293300 BAIAP2 H46962 PRNP AA455969 MME R98851 ST6GALNAC2 AA497051 GRHL1 R63971 LOC285958 AA028884 PCYOX1L AA701491 CMTM7 AA454864 GATA2 R32406 SOX4 N23606 ADARB1 AA489331 RNF126 AA463982 MAPKAPK2 AA455056 ITGB3 AA037229 SSX2IP H20847 SLC16A1 AA043133 PMVK H09914 UCK2 AA133778 ETNK2 H77535 NUP88 AA488609 FN1 R62612 DST H44784 NSDHL AA436425 KIAA1522 AA457115 FAM104A T58729 PSEN2 AA056325 PGM2L1 AA164836 ALPI AA190871 TLE3 W32778 R73672 OSBPL11 R22420 CPA4 AA016234 LASS6 W85843 AA436198 MPHOSPH10 AA504113 ZIC2 H40921 BIN1 AA453175 DTX4 AA487527 CORO2B N92783 SFRP1 T68892 CA2 H23187 TMEM158 AA127069 AKAP13 T50096 RCCD1 T96829 MPST AA461065 LIMA1 AA487557 PLEKHA7 R44496 LARP2 T82817 CYLD AA436200 RAB3A H14231 SFMBT2 R52082 AA427921 PTP4A1 AA703158 PLAC8 AA150263 MTX1 N69540 THOC3 AA599058 TBC1D9B AA018338 AADAT N75669 >8 4 2.8 2 1.4 1 1.4 2 2.8 4 >8 TGFB1 R36467 RABGAP1L H10709 H92588 Fold Fold POMT1 R37635 ARVCF H17975 Repression Induction AP1G2 T49401 MBL2 T69359 DUS1L AA599073 PTPN13 R85643 TIGD3 H10344 C4orf29 W91885 C4orf30 R00166 AA284249 Bolton_et_al._Supplemental_Figure2

134,532,000 134,535,000 134,538,000 134,541,000 SGK Probe: -375 to +544 DHS2 DHS1

+946 +1 ARE -4,579 Xba I Xba I Vehicle Androgen DNAse I: 0 minutes 0 minutes

• 5.5 kb fragment (-4,579 to +946)

2.1 kb DHS1 (-1,174 to +946)

1.0 kb DHS2 (+1 to +946) Bolton_et_al._Supplemental_Figure3 A

B 15% 44% Repressed Induced 26 154 3 20 16 126 20 40 Total AREs 65 340 35% 6% Total ARGs 44 128 AREs/ARG 1.5+1.1 2.7+1.8 Bolton_et_al._Supplemental_Figure4