Schäfer et al.

Ing1 functions in DNA demethylation by directing Gadd45a to H3K4me3

Andrea Schäfer, Emil Karaulanov, Ulrike Stapf, Gabi Döderlein, and Christof Niehrs

Supplemental Information

Inventory

Supplemental Figure Legends Supplemental Figures Figure S1, related to Figure 1 Figure S2, related to Figure 2 Figure S3, related to Figure 2 Figure S4, related to Figure 3 Figure S5, related to Figure 3 Figure S6, related to Figure 6 Figure S7, related to Figure 7 Figure S8, Model Supplemental Tables Table S1, related to Figure 5 Table S2, related to Figure 7 Table S3, related to Figure 7 Supplemental Material and Methods

Schäfer et al.

Supplemental Figure Legends

Figure S1.

(A) SDS-PAGE and autoradiography of in vitro pull down assays using recombinant His- tagged annexinV (His-Ctrl, control) or Xenopus Gadd45a (His-G45a) proteins and in vitro translated 35S-labelled ING1b (wild-type or deletion constructs), or green fluorescent protein (GFP, Co). WT, wild-type; PIP, PCNA interacting domain; PB, partial bromodomain; PHD, plant homeodomain; W235A, pointmutation within the PHD domain.

(B) Luciferase reporter assays of HEK293T cells transiently transfected with empty vector (Co) or Xenopus Gadd45a (xG45a) and ING1b or its mutants (see scheme in (A)) along with in vitro methylated SV40 reporter plasmid.

(C) qPCR expression analysis of the indicated target genes was monitored in HEK293T cells transiently transfected with control (siCo), ING1b, ING1a or GADD45a (G45a) specific siRNA as for Fig. 1E.

(D-E) Luciferase reporter assays of HEK293T cells transiently transfected as indicated with empty vector (Co), mouse Gadd45a and mouse Ing1 (p31Ing1a/c and p37Ing1b) along with in vitro methylated rDNA promoter- (D) or pGL3-Luc reporter plasmid (SV40) (E).

(F-G) Histone H3- (F) or H3K4me3-ChIP (G) of two regions of the Oct4TK-GFP reporter spanning CpG -299 or the ATG (see scheme Fig. 1G) using HEK293T chromatin harvested 48h after transfection. ChIP using IgG served as negative control. ATG, translation start site.

Bar charts represent the mean of independent experiments (n=3) with error bars as ± SD.

Schäfer et al.

Figure S2.

(A) RKO cells were transiently transfected with indicated siRNAs. After 48h cell extracts were prepared and subjected to Western blot analysis. Conditions were as used for Fig.

2A-B and D.

(B) Bisulfite sequencing analysis of the region -160 to +80 of MAGEB2 (relative to the transcription start site). RKO cells were transiently transfected with control (top), ING1b

(middle) or GADD45a specific siRNA (bottom). Each line represents one clone. White and black circles, unmethylated and methylated CpG, respectively. The black box marks the 3 CpGs between -70 and -57 shown in Fig. 2B. Site -57 is also indicated in the diagram of the MAGEB2 5’upstream region. Letters a-d mark sites analyzed by ChIP.

(C) myc-ING1b- (left) or HA-GADD45a-ChIP (right) in RKO cells of the MAGEB2 sites indicated in the diagram in (B).

(D) HA-GADD45a- (left) or myc-ING1b-ChIP (right) of the MAGEB2 site “a” (see diagram in (B)) in RKO cells transiently transfected with the indicated siRNAs prior to

DNA transfection. Bars represent the mean of independent experiments (n=3) with error bars as ± SD.

Figure S3.

(A-B) Western blot (WB) analysis of in vitro pulldowns using biotinylated histone H3 peptides carrying the indicated modifications and nuclear extracts of HEK293T cells transfected with myc-ING1b or its mutants (see scheme Fig. S1A) alone (A) or with HA-

GADD45a (B).

Schäfer et al.

Figure S4.

(A) qPCR expression analysis as in Fig. 3C in MEFs of the indicated genotype 16h after

UV-irradiation with 20 or 40 J/m2 (UV+, ++). WT, wild-type MEFs.

(B) Diagram of the murine Mageb2 5’ upstream region. Letters a-h mark sites analyzed by ChIP in Fig. 4C-D. Region a, a’ and b include methylation-sensitive restriction enzyme sites as indicated and used for MS-PCR of Figs. 3D-F and 4B. Predicted transcription- (TSS) and the translation start sites (ATG) are marked.

(C) Basal Mageb2 and Gapdh promoter methylation levels in unirradiated knockout

MEFs of the experiments shown in Fig. 3E monitored by methylation-sensitive qPCR.

The analyzed Mage2 sites are indicated in (B).

Bar charts represent the mean of independent experiments (n=3) with error bars as ± SD.

Figure S5.

(A) H3K4me3-ChIP analysis of Mageb2 in MEFs from experiment Fig. 3A, B, D and F.

MEF cells were irradiated with 40 J/m2 and harvested after the indicated time points.

Analyzed sites are indicated in the scheme in Fig. S4B. ‘Co’, qPCR of an intergenic control region. Bars represent the mean of independent experiments (n=3) with error bars as ± SD.

(B) Western blot analysis for differentially methylated histone H3 proteins from MEFs transiently transfected with control or Wdr5 specific siRNA.

Schäfer et al.

Figure S6.

(A) qPCR expression analysis of the indicated target genes in HEK293T cells transiently transfected with the indicated siRNAs followed by transfection of the indicated genes.

(B-C) DNA methylation analysis of the regulatory regions of DHRS2 (B) and TAF7L (C) in HEK293T cells assessed by 454 bisulfite sequencing. The experiment is also shown in

Fig. 5D-E, here including samples expressing the ING1b'PHD mutant.

(D) HA-GADD45a-ChIP of the regulatory regions of selected target genes including the negative control region GAPDH and an intergenic control region (Co) in transiently transfected HEK293T cells.

(E) H3K4me3-ChIP of the regulatory regions of selected target genes including the negative control region GAPDH in HEK293T cells treated as in (A).

Bar charts represent the mean of independent experiments (n=3) with error bars as ± SD.

Figure S7.

(A) qPCR expression analysis of the indicated genes in MEFs of the indicated genotype.

WT, wild-type MEFs.

(B) Magnified view of the qPCR expression analysis of Fig. 7E of the indicated genes in wild-type MEFs transiently transfected with the indicated siRNAs.

Bar charts represent the mean of independent experiments (n=3) with error bars as ± SD.

Schäfer et al.

Figure S8.

Model for Gadd45a targeting by Ing1. Chromatin at the transcription start site contains

H3K4me3. Ing1 acts as adapter between H3K4me3 and Gadd45a, likely requiring additional unknown targeting factors. The nucleotide excision (NER) - or base excision-

(BER) repair machinery is engaged by Gadd45a and excises 5mC, which is replaced by unmethylated cytosine via DNA repair synthesis (not shown), thereby promoting DNA demethylation.

Schäfer_FigS1 A B PIP PB PHD 12 WT Co 'PIP 10 'PB xG45a 'N 8 'PHD W235A 6 * 4

prey 2 35 25 Co ING1b 'PHD W235A Input (10%) 15 C siCo siING1b siCo 35 1.2 siING1a 1.2 siG45a 25 siING1b His-G45a 1.0 1.0 15 0.8 0.8 35 0.6 0.6 25 His-Ctrl 0.4 0.4 15 0.2 0.2

ING1b ING1a Gadd45a D E Co rDNA Co SV40 35 mGadd45a 12 mGadd45a 30 10 25 8 20 6 15 4 10 5 2

Co Ing1b Ing1a/c Co Ing1b Ing1a/c p37 p31 p37 p31 F G 1.2 2.5 Co Co 1.0 G45a 2.0 G45a 0.8 ING1b ING1b G45a 1.5 G45a 0.6 +ING1b +ING1b 1.0 0.4 0.2 0.5

-299 ATG IgG (-299) -299 ATG IgG (-299) Schäfer_FigS2 A B TSS ATG -57 hMAGEB2 locus a b c d

-57

siCo ING1b 35

GADD45a 15 H3 15 siING1b

siGADD45a

C

1.0 0.3 Co Co 0.8 ING1b G45a ING1b+G45a G45a+ING1b 0.2 0.6

0.4 0.1 0.2

a b c d a b c d

D 0.3 siCo siING1b siCo siG45a 0.8 0.2

0.4 0.1 Schäfer_FigS3 A B

WB:G45a WB:ING1b 40 25 40 35 ING1b 35 G45a 25 35 ING1b'PHD 40 35 G45a + ING1b 25 15 G45a + 'N 25 35 G45a + 'PHD 25 25 40 G45a + W235A 35 Schäfer_FigS4 A

8 4.0 Gadd45a Co * ** Co Ing1a 7 UV+ * UV+ 6 3.0 UV++ UV++ * 5 2.0 4 3 1.0 2 1

n 6 o i Gadd45b * Ing1b s

s 5 1.0 e r 4 0.8 p x

e 3 0.6

e

v 2 0.4 i t a l 1 0.2 e r 1.5 3.0 Gadd45g Ing1c 2.5 1.0 2.0 1.5 * * 0.5 * ** 1.0 0.5

WT G45a -/- Ing1 -/- G45a -/- WT G45a -/- Ing1 -/- G45a -/- Ing1 -/- Ing1 -/-

B mMAGEB2 locus TSS ATG 1kb a a’ b c d e f g h

HhaI HhaI HpaII

C a a’ b Gapdh Mageb2

120 * n 100 * * o i t a

l 80 y h t 60 e m

40

% 20

WT G45a -/- Ing1 -/- G45a -/- Ing1 -/- Schäfer_FigS5

A

25 Co 4 h 20 8 h 24 h 15 IgG

10

5

a b c d e f g h Gapdh Co

Mageb2

B +UV

15 H3K4me3

15 H3K4me2

15 H3K4me1

15 H3 A Schäfer_FigS6 35 Co G45a ING1b 'PHD W235A 30 G45a+ING1b G45a+'PHD G45a+W235A 25 20 15 10 5

siCo siWDR5 siCo siWDR5 siCo siWDR5 DHRS2 TCEAL7 TAF7L B C 100 100 DHRS2 Co G45a ING1b G45a+ING1b Co TAF7L 'PHD G45a+'PHD 80 ING1b 80 G45a 60 60 G45a+ING1b 'PHD 40 40 G45a+'PHD 20 20

CpG: 1 2 3 4 5 CpG: 1 2 3 4 D 1.6 Co G45a 1.2 G45a + ING1b G45a +'PHD 0.8 G45a + W2345A 0.4

E DHRS2 TCEAL7 TAF7L GAPDH Co 5 DHRS2 4 TCEAL7 TAF7L 3 GAPDH

2

1

Co G45a ING1b 'PHD W235A G45a + G45a + G45a + Co G45a ING1b G45a ING1b 'PHD W235A +ING1b siCo siWDR5 Schäfer_FigS7

A B

1.8 1.2 WT G45a -/- siCo siWdr5 1.6 Ing1-/- DKO 1.0 1.4 1.2 0.8 1.0 *** 0.6 ** 0.8 0.6 0.4 0.4 0.2 *** 0.2

Gadd45a Ing1a Ing1b Wdr5 Cxcl1 Hoxd8

Schäfer_FigS8

Additional targeting factors?

G45a G C C G NER/BER Schäfer et al.

Table S1 Differentially expressed microarray probes and genes in the HEK293T gain-of- function experiment (GEO series record GSE43317). Shown are the mean expression fold changes in each sample relative to the control and the significant changes (see Methods) are marked in bold:

PROBE_ID SYMBOL GENE_ID ACCESSION G45a ING1b G45a+ING1b ǻPHD G45a+ǻPHD

ILMN_1794213 ABHD14A 25864 NM_015407.3 0.296 1.017 0.442 0.732 0.357 ILMN_1771348 ACN9 57001 NM_020186.1 0.401 0.945 0.365 1.127 0.567 ILMN_1671703 ACTA2 59 NM_001613.1 0.334 0.600 0.331 0.684 0.359 ILMN_1716264 ANKRD1 27063 NM_014391.2 1.885 4.110 8.643 1.000 1.681 ILMN_1740938 APOE 348 NM_000041.2 0.456 1.184 0.791 0.716 0.660 ILMN_1711120 ARC 23237 NM_015193.3 1.000 6.226 10.435 1.000 1.208 ILMN_2188119 ARL16 339231 NM_001040025.1 1.323 1.232 2.043 1.167 1.157 ILMN_2334765 ARMCX3 51566 NM_177947.2 1.757 1.492 1.897 2.006 2.055 ILMN_1688180 ASPSCR1 79058 XM_001132706.1 0.134 1.098 0.184 0.888 0.237 ILMN_1810235 ATP6V1E2 90423 NM_080653.3 0.763 0.637 0.494 0.526 0.257 ILMN_1703123 AXUD1 64651 NM_033027.2 2.073 1.230 1.787 1.280 1.740 ILMN_2210581 B3GAT3 26229 NM_012200.2 1.350 1.785 2.051 1.180 1.719 ILMN_1651285 BCL6B 255877 NM_181844.2 0.254 1.002 0.262 0.870 0.277 ILMN_1719165 BRMS1 25855 NM_015399.3 1.576 1.460 2.252 1.536 2.025 ILMN_1804656 C12orf62 84987 NM_032901.2 0.431 0.891 0.504 1.026 0.621 ILMN_2393450 C14orf173 64423 NM_022489.2 0.256 0.868 0.269 0.938 0.390 ILMN_1686082 C14orf79 122616 NM_174891.3 0.731 0.912 0.384 0.943 0.634 ILMN_1797155 C17orf75 64149 NM_022344.2 0.372 0.666 0.224 0.351 0.344 ILMN_1730818 C19orf30 284424 NM_174947.2 0.798 6.386 10.242 0.622 0.604 ILMN_1661595 C1orf53 388722 NM_001024594.1 0.479 0.733 0.597 0.585 0.373 ILMN_2049727 C20orf111 51526 NM_016470.6 1.760 1.410 2.113 1.326 1.962 ILMN_1774265 C2orf82 389084 NM_206895.1 3.447 1.546 2.917 0.477 1.569 ILMN_1668629 C4orf48 401115 XM_937968.2 0.400 1.003 0.406 1.038 0.483 ILMN_3239531 C4orf48 401115 NM_001141936.1 0.410 0.821 0.502 0.512 0.443 ILMN_1776788 C5orf41 153222 NM_153607.1 2.847 1.948 3.286 1.413 2.439 ILMN_1804895 C7orf53 286006 NM_182597.1 5.178 5.177 13.338 4.125 4.149 ILMN_1790315 C7orf63 79846 NM_001039706.1 1.806 1.049 1.055 1.503 2.096 ILMN_1656369 C8orf4 56892 NM_020130.3 1.000 1.000 4.901 1.000 1.000 ILMN_1762407 CABLES2 81928 NM_031215.2 0.341 1.275 1.252 0.783 0.600 ILMN_2286014 CATSPER2 117155 NM_172097.1 1.273 1.162 2.363 0.992 1.075 ILMN_3248676 CBWD3 445571 NM_201453.2 1.561 2.036 2.172 1.876 1.614 ILMN_2122511 CCBE1 147372 NM_133459.1 1.257 1.077 2.143 0.945 0.917 ILMN_1781234 CCDC22 28952 NM_014008.2 0.848 0.237 0.212 0.942 0.776 ILMN_2166524 CCNYL1 151195 NM_152523.1 1.936 2.356 2.559 1.707 2.367 ILMN_2396444 CD14 929 NM_001040021.1 1.805 2.095 4.012 1.944 2.900 ILMN_1765704 CDC2L1 984 NM_033492.1 2.053 1.886 2.065 2.094 2.245 ILMN_1778557 CDC2L5 8621 NM_003718.3 0.430 0.792 0.457 0.952 0.544 ILMN_1660654 CDCA2 157313 NM_152562.2 1.498 1.671 2.377 1.540 1.719 ILMN_1748883 CDKN2D 1032 NM_079421.2 1.727 2.090 2.254 1.454 1.737 ILMN_1723418 CEL 1056 NM_001807.3 0.688 2.922 0.815 0.810 0.683 ILMN_1777190 CFD 1675 NM_001928.2 0.497 0.804 0.614 0.675 0.424 ILMN_1734176 CGA 1081 NM_000735.2 1.335 2.119 2.978 1.681 1.499 ILMN_1731609 CHMP6 79643 XM_001132548.1 0.671 0.634 0.474 0.584 0.657 ILMN_1758339 CSTF1 1477 NM_001033521.1 3.636 2.063 3.269 2.446 2.581 ILMN_1806951 CSTF3 1479 NM_001033506.1 2.067 1.296 1.612 1.775 2.223 ILMN_1744604 CYBA 1535 NM_000101.2 0.411 0.996 0.495 1.050 0.591 ILMN_2354478 CYFIP2 26999 NM_001037333.1 0.358 0.621 0.497 0.754 0.490 ILMN_2054607 CYP4V2 285440 NM_207352.2 0.391 0.722 0.544 0.640 0.481 ILMN_1733851 DACT3 147906 NM_145056.1 1.054 2.250 1.726 1.207 1.585 ILMN_1781721 DDX31 64794 NM_022779.7 0.458 0.826 0.376 0.861 0.538 ILMN_1725726 DHRS2 10202 NM_182908.3 2.140 31.219 37.488 1.695 3.838 ILMN_2384857 DHRS2 10202 NM_182908.3 1.000 61.704 76.322 1.590 2.520 ILMN_1775304 DNAJB1 3337 NM_006145.1 1.438 2.283 4.688 1.472 1.710 ILMN_1771622 DRD1IP 50632 NM_015722.2 0.365 0.568 0.186 0.642 0.344 ILMN_2401878 DUSP10 11221 NM_144729.1 4.234 4.903 4.870 2.486 3.980 ILMN_1772796 DYNLL2 140735 NM_080677.1 1.269 1.494 1.570 1.709 2.386 ILMN_2408039 EEF1D 1936 NM_032378.2 1.055 0.521 0.482 1.177 1.220 ILMN_1762899 EGR1 1958 NM_001964.2 1.036 4.000 9.850 1.328 1.181 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION G45a ING1b G45a+ING1b ǻPHD G45a+ǻPHD

ILMN_1739222 ETV5 2119 NM_004454.1 3.761 1.254 3.839 1.000 4.351 ILMN_1790562 EYA3 2140 NM_001990.2 2.536 1.533 1.747 1.474 2.377 ILMN_1773780 FAM173A 65990 NM_023933.1 0.373 0.983 0.389 1.134 0.546 ILMN_1739199 FAM39DP 374666 NR_003659.1 0.375 1.230 0.459 1.290 0.643 ILMN_2123559 FAM73A 374986 NM_198549.1 1.303 1.194 2.491 1.116 1.187 ILMN_1670322 FCHO2 115548 NM_138782.1 0.647 0.589 0.420 0.500 0.597 ILMN_1655525 FLCN 201163 NM_144606.4 3.755 1.483 1.720 1.467 3.487 ILMN_1805665 FLRT3 23767 NM_198391.1 0.416 1.152 0.714 0.698 0.561 ILMN_1751607 FOSB 2354 NM_006732.1 0.471 4.013 8.621 1.612 0.884 ILMN_1716400 FOXM1 2305 NM_202003.1 0.484 0.913 0.437 0.910 0.577 ILMN_1663569 FTCD 10841 NM_206965.1 1.000 2.343 6.293 1.000 1.000 ILMN_2389273 FXR1 8087 NM_005087.2 0.411 1.157 0.431 1.313 0.628 ILMN_2151281 GABARAPL1 23710 NM_031412.2 1.923 1.272 1.560 1.547 2.041 ILMN_1718977 GADD45B 4616 NM_015675.2 0.818 4.382 7.058 1.842 1.518 ILMN_1784749 GAS6 2621 NM_000820.1 0.711 0.562 0.432 0.885 0.805 ILMN_1779558 GAS6 2621 NM_000820.1 0.748 0.589 0.491 0.935 0.758 ILMN_1709674 GFPT2 9945 NM_005110.1 1.312 1.394 1.682 2.061 2.157 ILMN_1680730 GGTLC1 92086 NM_178311.1 55.967 1.000 56.538 1.000 18.846 ILMN_1760922 GIT2 9815 NM_014776.2 2.287 1.527 1.692 1.909 1.955 ILMN_1703565 GLTSCR2 29997 NM_015710.3 0.934 0.319 0.285 1.029 0.999 ILMN_2383419 GMEB1 10691 NM_024482.1 2.247 1.389 1.643 1.111 1.625 ILMN_1727761 GMEB1 10691 NM_024482.1 2.306 1.456 1.671 1.028 1.824 ILMN_1725271 GPR3 2827 NM_005281.2 3.321 3.251 6.005 1.421 3.348 ILMN_1666206 GSDMB 55876 NM_001042471.1 1.727 1.208 1.686 1.620 2.522 ILMN_2246548 GSTTP2 653399 NR_003082.1 1.447 1.261 2.444 1.379 1.154 ILMN_2211728 GUCA1B 2979 NM_002098.3 2.572 2.040 2.466 1.939 1.964 ILMN_1708728 H2AFJ 55766 NM_177925.2 1.262 1.666 2.002 1.106 1.349 ILMN_1691926 HADH2 3028 NM_004493.1 0.410 0.918 0.489 1.023 0.596 ILMN_2121408 HBEGF 1839 NM_001945.1 1.657 2.396 3.333 1.578 1.918 ILMN_1741180 HEXDC 284004 NM_173620.2 0.452 0.860 0.390 0.436 0.457 ILMN_1651496 HIST1H2BD 3017 NM_138720.1 0.607 2.901 1.794 0.995 0.676 ILMN_1658702 HIST1H2BJ 8970 NM_021058.3 1.543 2.355 2.565 0.786 1.073 ILMN_1813314 HIST1H2BK 85236 NM_080593.1 1.271 1.341 2.535 0.907 0.919 ILMN_1751120 HIST1H4H 8365 NM_003543.3 0.925 7.366 4.568 1.228 0.661 ILMN_2144426 HIST2H2AA3 8337 NM_003516.2 1.550 2.596 3.326 0.879 1.307 ILMN_1659047 HIST2H2AA3 8337 NM_003516.2 1.530 2.412 3.336 0.951 1.419 ILMN_3242900 HIST2H2AA4 723790 NM_001040874.1 1.510 2.038 2.508 1.008 1.356 ILMN_1768973 HIST2H2AC 8338 NM_003517.2 1.356 1.920 2.300 0.977 1.152 ILMN_1732071 HIST2H2BE 8349 NM_003528.2 1.207 2.920 2.887 1.132 1.027 ILMN_1766499 HSPA2 3306 NM_021979.3 0.394 2.515 3.163 1.009 0.538 ILMN_1806165 HSPA6 3310 NM_002155.3 2.200 6.395 11.842 1.178 1.777 ILMN_1755620 IER5L 389792 NM_203434.2 0.556 2.495 3.656 1.538 0.913 ILMN_1784178 IFT172 26160 NM_015662.1 0.190 1.055 0.488 0.901 0.352 ILMN_2132982 IGFBP5 3488 NM_000599.2 0.496 0.920 0.634 0.625 0.525 ILMN_2085722 ING2 3622 NM_001564.2 0.928 0.188 0.127 1.195 1.076 ILMN_1744212 INPP5D 3635 NM_005541.3 0.961 6.248 0.961 0.961 0.961 ILMN_1660844 INTS4 92105 NM_033547.3 0.463 1.317 0.586 0.942 0.594 ILMN_1745471 IRF9 10379 NM_006084.4 1.246 2.003 1.285 1.516 1.318 ILMN_1659913 ISG20 3669 NM_002201.4 1.178 1.879 2.712 0.851 1.366 ILMN_1687092 KBTBD4 55709 NM_018095.3 1.443 1.764 2.013 1.151 1.135 ILMN_1786843 KCTD13 253980 NM_178863.2 1.378 1.970 2.759 1.548 1.679 ILMN_2163070 KHDC1 80759 NM_030568.3 0.575 0.547 0.220 0.424 0.240 ILMN_1693233 KIAA0513 9764 NM_014732.2 2.074 3.915 4.032 2.752 1.827 ILMN_1669433 KIAA0913 23053 NM_015037.2 1.751 1.249 1.532 1.446 2.035 ILMN_2158003 KIAA1683 80726 NM_025249.1 1.000 1.000 6.879 1.000 1.000 ILMN_2415979 KIAA1751 85452 NM_001080484.1 1.166 1.141 2.331 0.994 0.960 ILMN_1716553 KIF23 9493 NM_138555.1 2.640 1.180 1.979 1.556 2.278 ILMN_3263974 KRT18P13 392371 XM_001726959.1 0.883 0.285 0.179 0.546 0.774 ILMN_1791721 KRTAP21-2 337978 NM_181617.1 2.491 1.000 6.051 1.036 1.424 ILMN_1723978 LGALS1 3956 NM_002305.3 0.978 3.651 3.329 0.772 0.895 ILMN_1754969 LMCD1 29995 NM_014583.2 0.944 2.584 2.701 0.403 0.634 ILMN_3189621 LOC100128221 100128221 XM_001713928.1 0.402 0.589 0.329 0.554 0.193 ILMN_3191668 LOC100129236 100129236 XM_001714142.1 1.000 4.683 4.608 1.000 1.000 ILMN_3261387 LOC100129236 100129236 XM_001716550.1 1.000 11.483 10.164 1.397 1.000 ILMN_3238283 LOC100130123 100130123 XM_001726844.1 1.791 1.337 2.508 1.350 2.235 ILMN_3239135 LOC100132391 100132391 XM_001716455.1 1.099 1.211 2.051 0.926 1.041 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION G45a ING1b G45a+ING1b ǻPHD G45a+ǻPHD

ILMN_3243644 LOC100132564 100132564 XM_001713808.1 0.753 2.574 4.739 1.838 2.505 ILMN_3237404 LOC100132585 100132585 XM_001722111.1 1.487 1.340 2.808 1.122 1.137 ILMN_1710954 LOC283932 283932 NM_175901.3 3.011 1.262 2.101 1.205 2.483 ILMN_1674983 LOC387841 387841 XM_932678.1 1.685 1.206 2.210 1.177 1.284 ILMN_3280565 LOC389342 389342 XM_945799.3 0.934 0.909 0.842 0.364 0.393 ILMN_3294134 LOC389765 389765 XM_001720643.1 1.211 1.168 2.674 1.035 1.083 ILMN_3246247 LOC399491 399491 XR_041580.1 2.017 1.248 1.271 1.515 2.181 ILMN_3291472 LOC442727 442727 XR_017503.2 0.469 0.658 0.444 0.837 0.622 ILMN_3292082 LOC642367 642367 XR_038808.1 1.985 1.731 3.096 1.530 1.877 ILMN_1665290 LOC643995 643995 XM_934410.1 2.907 1.757 2.302 2.113 2.321 ILMN_1727165 LOC644852 644852 XM_934218.1 1.311 1.043 2.188 1.021 0.962 ILMN_1721651 LOC646463 646463 XM_001130106.1 2.215 1.553 2.048 1.531 2.820 ILMN_1729115 LOC651816 651816 XM_941060.1 0.485 1.015 0.525 1.213 0.711 ILMN_1800131 LOC652826 652826 XM_942509.2 1.918 1.432 2.122 1.444 1.711 ILMN_1701882 LOC653820 653820 XM_930579.2 2.000 1.449 1.824 1.541 1.614 ILMN_3305993 LOC728602 728602 XR_039532.1 1.882 0.911 2.633 0.883 2.750 ILMN_3234615 LOC728650 728650 XR_042473.1 0.783 0.144 0.149 0.767 0.684 ILMN_1699253 LOC729317 729317 XM_001133585.1 0.387 0.816 0.417 0.829 0.636 ILMN_1737561 LOC88523 88523 NM_033111.2 2.461 1.006 1.403 1.114 1.451 ILMN_1720452 LONRF3 79836 NM_001031855.1 2.103 1.091 1.400 1.479 2.364 ILMN_1668863 LYPD1 116372 NM_144586.5 0.444 0.574 0.411 0.593 0.491 ILMN_1689257 MAEA 10296 NM_001017405.1 0.136 1.134 0.136 1.372 0.136 ILMN_2352580 MBD1 4152 NM_015844.1 1.560 1.816 2.071 1.884 2.769 ILMN_1718171 MED26 9441 NM_004831.3 1.911 1.712 2.216 1.725 2.260 ILMN_1728360 MED29 55588 NM_017592.1 0.203 1.168 0.284 0.809 0.287 ILMN_2111237 MN1 4330 NM_002430.2 0.374 0.750 0.263 0.777 0.473 ILMN_1658486 MRPL54 116541 NM_172251.1 0.366 0.860 0.417 0.767 0.402 ILMN_2297864 MTMR14 64419 NM_001077525.1 1.424 1.515 2.125 1.443 1.871 ILMN_1657550 MVD 4597 NM_002461.1 1.190 1.792 2.217 1.428 1.649 ILMN_2214678 MXD1 4084 NM_002357.2 1.245 1.917 2.621 1.640 1.824 ILMN_1731215 MYBPHL 343263 NM_001010985.1 1.000 9.067 1.000 1.000 1.000 ILMN_3234089 N4BP2L2 10443 NM_033111.3 2.397 0.958 1.348 1.327 1.584 ILMN_1767139 NDUFA13 51079 NM_015965.4 0.228 1.015 0.233 1.043 0.307 ILMN_1785711 NEDD8 4738 NM_006156.2 1.578 1.402 1.406 2.014 1.672 ILMN_1763144 NEU1 4758 NM_000434.2 1.659 2.338 2.953 1.556 2.627 ILMN_1704305 NIP7 51388 NM_016101.3 0.451 0.969 0.486 0.980 0.545 ILMN_1725612 NUP50 10762 NM_007172.3 2.101 1.183 1.618 1.276 2.037 ILMN_2358652 NXF1 10482 NM_006362.4 1.643 1.666 2.485 1.488 1.969 ILMN_1705783 NXF1 10482 NM_001081491.1 1.661 1.631 2.892 1.462 2.001 ILMN_1706652 OGG1 4968 NM_002542.4 1.114 0.250 0.250 1.185 0.923 ILMN_2055156 PAG1 55824 NM_018440.3 0.420 0.690 0.540 0.638 0.445 ILMN_1683023 PDGFC 56034 NM_016205.1 0.642 0.646 0.442 0.633 0.576 ILMN_1810191 PLA2G4C 8605 NM_003706.1 1.294 1.232 3.260 0.771 0.701 ILMN_1652580 POLD1 5424 NM_002691.1 0.550 0.924 0.484 0.879 0.606 ILMN_2364384 PPARG 5468 NM_138712.3 0.299 0.528 0.256 0.656 0.334 ILMN_2395389 PSMC4 5704 NM_006503.2 1.893 1.591 2.041 1.763 1.834 ILMN_1687887 PSMC4 5704 NM_006503.2 2.242 1.628 2.408 2.063 2.437 ILMN_2105253 PTGR2 145482 NM_152444.1 1.227 1.169 2.707 1.052 0.991 ILMN_2399140 RAB5C 5878 NM_004583.2 1.814 1.464 2.106 2.054 2.159 ILMN_1740426 RASD1 51655 NM_016084.3 1.250 4.547 12.663 1.595 1.628 ILMN_1755657 RASIP1 54922 NM_017805.2 1.178 2.030 1.670 0.915 0.934 ILMN_3227341 RFPL4A 342931 XM_001719234.1 1.207 1.434 4.666 0.934 1.209 ILMN_1808404 RHBDF1 64285 NM_022450.2 2.087 1.378 1.405 1.404 2.245 ILMN_2053538 RHBDL2 54933 NM_017821.3 1.233 1.143 2.429 1.003 1.090 ILMN_2404135 RIOK3 8780 NM_003831.2 2.080 1.360 1.685 1.404 2.127 ILMN_3234762 RN5S9 100169760 NR_023371.1 0.905 22.480 28.344 10.613 6.756 ILMN_1651838 RND1 27289 NM_014470.2 1.000 5.782 9.369 1.000 1.073 ILMN_1812327 RNF19A 25897 NM_183419.1 1.383 6.437 8.445 0.677 0.677 ILMN_3241878 RNU6ATAC 100151684 NR_023344.1 0.608 4.901 3.470 1.289 0.879 ILMN_1684306 S100A4 6275 NM_019554.2 0.278 2.539 0.278 0.278 0.278 ILMN_1688780 S100A4 6275 NM_019554.2 1.187 5.030 1.888 0.754 0.696 ILMN_1776674 SAC3D1 29901 NM_013299.3 0.294 1.101 0.294 1.003 0.355 ILMN_1754458 SDHALP1 255812 NR_003264.1 2.822 1.847 2.114 2.273 4.491 ILMN_1758056 SELK 58515 NM_021237.3 3.645 5.099 9.920 2.051 4.812 ILMN_1803744 SELS 55829 NM_018445.4 0.431 1.259 0.514 1.219 0.693 ILMN_1794017 SERTAD1 29950 NM_013376.3 1.248 4.034 3.867 0.968 1.332 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION G45a ING1b G45a+ING1b ǻPHD G45a+ǻPHD

ILMN_1791728 SLC25A25 114789 NM_052901.2 1.990 1.696 2.341 1.251 2.035 ILMN_2120247 SLC2A10 81031 NM_030777.3 0.469 0.593 0.518 0.470 0.451 ILMN_2410938 SMOC1 64093 NM_001034852.1 0.420 0.866 0.618 0.964 0.648 ILMN_1785618 SMTN 6525 NM_006932.3 1.210 2.938 2.436 1.178 1.156 ILMN_3241140 SNORA14B 677802 NR_002956.1 2.256 1.955 4.364 1.654 1.886 ILMN_3241798 SNORA41 619569 NR_002590.1 2.009 1.942 2.082 1.645 1.777 ILMN_3238078 SNORA45 677826 NR_002977.1 1.879 1.999 2.432 2.569 2.539 ILMN_3235404 SNORA57 692158 NR_004390.1 0.901 2.856 2.536 2.152 1.979 ILMN_3235969 SNORA9 677798 NR_002952.1 1.419 2.032 4.275 2.777 1.727 ILMN_1784328 SNORD25 9303 NR_002565.1 1.719 1.518 1.669 1.973 2.542 ILMN_3239574 SNORD3A 780851 NR_006880.1 0.601 3.229 4.126 2.461 2.142 ILMN_3241034 SNORD3C 780853 NR_006881.1 0.738 6.518 6.548 4.055 3.025 ILMN_3242315 SNORD3D 780854 NR_006882.1 0.746 3.260 3.647 2.202 1.946 ILMN_3238662 SNORD89 692205 NR_003070.1 1.737 1.477 1.598 2.194 1.871 ILMN_1793410 SNTB1 6641 NM_021021.2 0.511 0.414 0.307 0.535 0.488 ILMN_1653415 SPANXA2 728712 NM_145662.2 1.000 7.547 1.428 1.000 1.000 ILMN_1667948 SPATA18 132671 NM_145263.2 0.479 0.599 0.431 0.844 0.494 ILMN_1815283 SULT1A3 6818 NM_003166.3 1.700 2.579 2.113 1.663 1.822 ILMN_3250899 SULT1A3 6818 NM_177552.2 2.676 4.009 3.955 2.103 2.398 ILMN_2336133 SULT1A4 445329 NM_001017391.1 1.419 2.037 1.706 1.381 1.276 ILMN_2336130 SULT1A4 445329 NM_001017391.1 1.323 2.233 2.019 1.609 1.404 ILMN_1717934 SYT11 23208 NM_152280.2 1.094 1.960 2.579 0.842 0.978 ILMN_2160210 TACSTD1 4072 NM_002354.1 2.559 1.586 1.958 1.223 1.528 ILMN_1790953 TBCB 1155 NM_001281.2 0.319 1.050 0.405 0.974 0.362 ILMN_1744795 TBL1X 6907 NM_005647.2 0.780 0.379 0.432 0.871 0.743 ILMN_1753525 TCEAL7 56849 NM_152278.2 2.412 11.004 15.377 0.612 0.960 ILMN_1662619 TFPI 7035 NM_006287.4 2.049 0.936 1.372 1.015 1.859 ILMN_1707124 TFPI 7035 NM_006287.4 2.344 1.009 1.421 1.099 1.722 ILMN_3249244 TMEM106A 113277 NM_145041.1 1.590 1.416 2.230 1.243 1.347 ILMN_3245912 TMEM59L 25789 NM_012109.2 1.150 1.429 2.339 1.097 1.644 ILMN_1689004 TNFRSF12A 51330 NM_016639.1 3.501 1.586 2.457 1.822 3.298 ILMN_1796949 TPX2 22974 NM_012112.4 0.450 1.079 0.370 1.343 0.430 ILMN_1696160 TRQ1 7228 NR_000037.1 1.331 2.427 7.071 0.880 1.393 ILMN_1674967 TSGA10 80705 NM_025244.1 0.755 5.108 3.026 0.438 0.509 ILMN_2347298 TSPYL2 64061 NM_022117.1 1.590 2.167 2.236 2.281 1.934 ILMN_1693635 TSPYL2 64061 NM_022117.1 1.227 1.820 2.398 1.498 1.797 ILMN_1657554 TSPYL2 64061 NM_022117.1 1.288 2.113 2.470 1.937 1.668 ILMN_1682818 TTLL3 26140 NM_015644.3 1.875 1.661 2.045 1.976 1.901 ILMN_2323816 TTLL8 164714 NM_001080447.1 4.349 1.000 1.737 1.000 1.000 ILMN_1791726 TUBB3 10381 NM_006086.2 1.027 2.771 5.686 0.877 1.198 ILMN_1781374 TUFT1 7286 NM_020127.1 1.363 2.067 2.243 1.256 1.829 ILMN_1676955 TYK2 7297 NM_003331.3 1.241 1.548 1.570 0.399 0.386 ILMN_3298694 TYW1B 441250 XR_015176.2 1.406 2.006 2.180 1.372 1.528 ILMN_1674703 UBE1DC1 79876 NM_198329.1 0.652 0.498 0.400 0.735 0.639 ILMN_2217289 UBE2S 27338 NM_014501.2 1.233 2.232 4.885 0.875 1.976 ILMN_1719785 UCK1 83549 NM_031432.1 0.157 0.886 0.157 0.749 0.157 ILMN_1679417 UPF2 26019 NM_080599.1 1.244 2.775 2.901 1.722 1.994 ILMN_1697227 USP36 57602 NM_025090.2 1.906 1.551 2.274 1.276 1.666 ILMN_1667295 VASN 114990 NM_138440.2 1.659 7.950 8.857 1.728 3.044 ILMN_1684886 VCX 26609 NM_013452.2 1.000 2.897 9.363 1.000 1.127 ILMN_1706028 VCX2 51480 NM_016378.2 1.776 3.368 6.430 2.033 2.325 ILMN_2366642 VCX3A 51481 NM_016379.2 1.775 4.960 11.645 1.767 3.149 ILMN_2166716 VCX-C 425054 NM_001001888.1 1.434 2.069 10.374 1.000 1.000 ILMN_1757497 VGF 7425 NM_003378.2 1.722 4.811 13.047 1.167 1.722 ILMN_2270845 WDR74 54663 NM_018093.1 1.424 1.172 2.099 1.291 1.421 ILMN_1800317 WNT5A 7474 NM_003392.3 0.407 0.758 0.569 0.738 0.513 ILMN_1790807 XPC 7508 NM_004628.3 0.523 1.067 0.499 1.020 0.506 ILMN_1694671 ZFAND2A 90637 NM_182491.1 1.486 1.575 2.940 1.058 1.901 ILMN_1720829 ZFP36 7538 NM_003407.2 1.569 1.698 2.057 1.137 1.624 ILMN_1692145 ZNF14 7561 NM_021030.2 1.276 1.284 2.128 1.154 1.071 ILMN_1674399 ZNF143 7702 NM_003442.4 1.801 2.031 2.547 1.529 1.783 ILMN_1807514 ZNF394 84124 NM_032164.2 1.856 1.717 2.246 2.112 2.379 ILMN_2137066 ZNF7 7553 NM_003416.1 0.471 0.930 0.325 1.108 0.608 ILMN_1791820 ZNF768 79724 NM_024671.3 0.435 0.906 0.385 1.164 0.626 ILMN_1734608 ZNF77 58492 NM_021217.1 1.281 2.115 2.524 1.413 1.724 ILMN_1749606 ZNF778 197320 NM_182531.2 2.562 3.497 6.043 1.302 3.072 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION G45a ING1b G45a+ING1b ǻPHD G45a+ǻPHD

ILMN_3300358 ZNF84 7637 NM_003428.4 1.232 1.451 2.334 0.726 0.937 ILMN_1789410 ZSCAN21 7589 NM_145914.2 0.435 1.447 0.512 1.114 0.685 ILMN_1870111 - - AK123449 3.805 1.322 2.296 2.317 4.113 ILMN_1851169 - - CB984746 2.297 1.673 2.519 1.692 1.789 ILMN_1817377 - - CD172175 1.951 1.572 2.759 1.606 1.209 ILMN_1856058 - - AW340271 2.423 3.106 3.577 2.509 4.766 ILMN_1908824 - - U62823 1.407 4.889 4.231 1.585 1.664 ILMN_1884160 - - BX103929 1.490 2.999 5.970 1.575 1.755

Note: By using alternative, less-stringent analysis parameters, several additional putative Gadd45a+ING1b inducible genes were identified. One of them, TAF7L, was tested by qPCR and further studied in methylation and ChIP experiments.

Significantly DOWN-regulated genes in each individual sample:

# G45a (GADD45a) : ABHD14A, ACN9, ACTA2, APOE, ASPSCR1, BCL6B, C12orf62, C14orf173, C4orf48, CABLES2, CYBA, CYFIP2, CYP4V2, DDX31, FAM173A, FAM39DP, FLRT3, FXR1, HADH2, IFT172, IGFBP5, INTS4, LOC442727, LOC651816, LOC729317, MAEA, MED29, MRPL54, NIP7, PAG1, PPARG, SAC3D1, SELS, SLC2A10, SMOC1, TBCB, UCK1, WNT5A, ZNF7, ZSCAN21

# ING1b : CCDC22, GLTSCR2, ING2, LOC728650, TBL1X

# G45a+ING1b : ACN9, ACTA2, ASPSCR1, BCL6B, C14orf173, C14orf79, C17orf75, C4orf48, CCDC22, CDC2L5, CHMP6, DDX31, DRD1IP, EEF1D, FAM173A, FAM39DP, FCHO2, FOXM1, FXR1, GAS6, GLTSCR2, HADH2, HEXDC, ING2, KHDC1, KRT18P13, LOC442727, LOC728650, LOC729317, LYPD1, MAEA, MED29, MN1, MRPL54, NDUFA13, NIP7, OGG1, PDGFC, POLD1, SAC3D1, SNTB1, SPATA18, TBCB, TBL1X, TPX2, UBE1DC1, UCK1, XPC, ZNF7, ZNF768

# ǻPHD (ING1bǻPHD) : LOC389342, TYK2

# G45a+ǻPHD : ACTA2, ASPSCR1, ATP6V1E2, BCL6B, C14orf173, C1orf53, C4orf48, CFD, CYP4V2, LOC100128221, LOC389342, MAEA, MED29, MRPL54, PAG1, SAC3D1, SLC2A10, TBCB, UCK1

Significantly UP-regulated genes in each individual sample:

# G45a (GADD45a) : AXUD1, C2orf82, CDC2L1, CSTF1, CSTF3, EYA3, FLCN, GGTLC1, GIT2, GMEB1, GUCA1B, KIF23, LOC399491, LOC643995, LOC646463, LOC653820, LOC88523, LONRF3, N4BP2L2, NUP50, PSMC4, RHBDF1, RIOK3, SDHALP1, TACSTD1, TFPI, TNFRSF12A, TTLL8

# ING1b : ARC, C19orf30, CDKN2D, CEL, DACT3, DHRS2, DNAJB1, DUSP10, EGR1, FOSB, GADD45B, HBEGF, HIST1H2BD, HIST1H2BJ, HIST2H2AA3, HIST2H2BE, HSPA6, INPP5D, IRF9, LGALS1, LMCD1, LOC100129236, LOC100132564, MYBPHL, NEU1, RASIP1, RN5S9, RND1, RNF19A, S100A4, SERTAD1, SNORA57, SPANXA2, SULT1A3, SULT1A4, TCEAL7, TUBB3, TUFT1, TYW1B, UPF2, VASN, VGF, ZNF77

# G45a+ING1b : ANKRD1, ARC, ARL16, B3GAT3, BRMS1, C19orf30, C20orf111, C7orf53, C8orf4, CATSPER2, CBWD3, CCBE1, CCNYL1, CD14, CDC2L1, CDCA2, CDKN2D, CGA, CSTF1, DHRS2, DNAJB1, DUSP10, EGR1, ETV5, FAM73A, FOSB, FTCD, GADD45B, GGTLC1, GPR3, GSTTP2, GUCA1B, H2AFJ, HBEGF, HIST1H2BJ, HIST1H2BK, HIST1H4H, HIST2H2AA3, HIST2H2AA4, HIST2H2AC, HIST2H2BE, HSPA2, HSPA6, IER5L, ISG20, KBTBD4, KCTD13, KIAA0513, KIAA1683, KIAA1751, KRTAP21-2, LGALS1, LMCD1, LOC100129236, LOC100130123, LOC100132391, LOC100132564, LOC100132585, LOC283932, LOC387841, LOC389765, LOC642367, LOC644852, LOC652826, MED26, MTMR14, MVD, MXD1, NEU1, NXF1, PLA2G4C, PSMC4, PTGR2, RAB5C, RASD1, RFPL4A, RHBDL2, RN5S9, RND1, RNF19A, RNU6ATAC, SELK, SERTAD1, SLC25A25, SMTN, SNORA14B, SNORA41, SNORA45, SNORA57, SNORA9, SNORD3A, SNORD3C, SNORD3D, SULT1A3, SYT11, TCEAL7, TMEM106A, TMEM59L, TNFRSF12A, TRQ1, TSGA10, TSPYL2, TTLL3, TUBB3, TUFT1, TYW1B, UBE2S, USP36, VCX, VCX2, VCX3A, VCX-C, VGF, WDR74, ZFAND2A, ZFP36, ZNF14, ZNF143, ZNF394, ZNF77, ZNF778, ZNF84

# ǻPHD (ING1bǻPHD) : NEDD8, SNORD89

# G45a+ǻPHD : ARMCX3, C5orf41, C7orf63, CCNYL1, CDC2L1, DYNLL2, ETV5, GABARAPL1, GFPT2, GSDMB, KIAA0913, LOC100130123, LOC646463, LOC728602, LONRF3, MBD1, NEU1, NUP50, NXF1, PSMC4, RHBDF1, RN5S9, SDHALP1, SNORA45, SNORD25, TNFRSF12A, ZNF394 Schäfer et al.

Table S2 Differentially expressed microarray probes and genes in the MEF loss-of-function experiment (GEO series record GSE43318). Shown are the mean expression fold changes in each mutant relative to the wild-type and the significant changes (see Methods) are marked in bold:

PROBE_ID SYMBOL GENE_ID ACCESSION Gadd45a -/- Ing1 -/- DKO

ILMN_2593774 1190002H23Rik 66214 NM_025427.2 0.653 0.874 0.518 ILMN_2615431 1200009O22Rik 66873 NM_025817.3 0.890 0.816 0.454 ILMN_2625085 1700112C13Rik 74306 NM_183103.2 1.732 0.881 2.237 ILMN_2418811 2200002D01Rik 72275 - 1.796 1.042 1.705 ILMN_2720620 2310001H12Rik 69504 XM_901486.2 1.864 1.413 1.909 ILMN_1232900 2310001H12Rik 69504 XM_901486.2 2.813 1.075 2.087 ILMN_2897214 2310039E09Rik 68016 NM_026509.1 2.027 1.231 1.995 ILMN_2675922 2310047A01Rik 71918 XM_908180.3 0.780 1.013 0.649 ILMN_1253189 2610014I16Rik 66300 XM_001480001.1 1.313 1.122 2.038 ILMN_2741063 2810003C17Rik 108897 NM_145144.1 1.192 0.960 1.585 ILMN_2645865 2810022L02Rik 67198 NM_144882.3 0.731 0.694 0.493 ILMN_2673917 2810022L02Rik 67198 NM_144882.3 0.715 0.845 0.526 ILMN_2443618 2900026A02Rik 243219 NM_172884 1.937 1.166 2.344 ILMN_2882088 5430435G22Rik 226421 NM_145509.1 0.848 0.908 0.622 ILMN_2489147 6330407I18Rik 70710 - 1.361 1.087 1.586 ILMN_2470131 6720475J19Rik 68157 XM_001474896.1 1.154 1.090 1.750 ILMN_2756704 9130213B05Rik 231440 NM_145562.2 2.418 1.791 3.096 ILMN_1245549 9930013L23Rik 80982 AK018112 1.288 1.090 2.058 ILMN_2522884 9930105H17Rik 100669 - 1.145 1.213 1.528 ILMN_2839745 A230050P20Rik 319278 NM_175687.1 0.681 0.426 0.365 ILMN_2447991 A730054J21Rik 320862 - 0.614 0.723 0.583 ILMN_2514655 Abca3 27410 NM_013855.2 0.826 0.784 0.571 ILMN_2918499 Abcb1b 18669 NM_011075.1 1.866 1.215 1.689 ILMN_1253008 Acat2 110460 NM_009338.3 0.789 0.960 0.628 ILMN_2830611 Accn3 171209 NM_183000.1 2.084 1.279 4.807 ILMN_3139875 Acot1 26897 NM_012006.2 0.714 0.506 0.532 ILMN_1254634 Acpl2 235534 NM_153420.2 1.325 1.043 1.625 ILMN_2734181 Acss2 60525 NM_019811.3 0.780 0.846 0.581 ILMN_1230599 Adam23 23792 NM_011780.2 0.878 0.778 0.634 ILMN_1234413 Adamts12 239337 NM_175501 1.271 1.302 1.692 ILMN_2729103 Adamts2 216725 NM_175643.2 0.573 0.672 0.536 ILMN_1226259 Adamts2 216725 NM_175643.2 0.587 0.758 0.574 ILMN_1221851 Adamts2 216725 NM_175643.2 0.494 0.614 0.583 ILMN_1230152 Adamts4 240913 NM_172845.1 0.627 0.839 0.539 ILMN_1257724 Adamts9 101401 - 0.788 0.864 0.592 ILMN_2663428 Adamtsl3 269959 XM_194370.6 1.649 0.897 1.954 ILMN_2538422 Adap1 231821 NM_172723.4 1.802 1.563 2.149 ILMN_1258501 Adh1 11522 NM_007409.2 0.316 0.316 0.316 ILMN_2621448 Adh7 11529 NM_009626.3 0.531 0.584 0.462 ILMN_1242170 Adra2a 11551 NM_007417.2 1.216 0.891 1.742 ILMN_3086136 Agap1 347722 NM_001037136.1 0.685 0.714 0.615 ILMN_2729783 Ahrr 11624 NM_009644.2 1.843 0.914 2.387 ILMN_2683486 AI115600 102442 XM_001476259.1 0.594 0.746 0.559 ILMN_3160963 AI316807 102032 NM_001012667.1 0.795 0.485 0.617 ILMN_2667805 Ak1 11636 NM_021515.2 1.295 1.235 1.750 ILMN_2606804 Alcam 11658 NM_009655.1 1.538 1.272 2.320 ILMN_1237578 Aldh1a3 56847 AK043530 1.128 1.769 1.987 ILMN_2761436 Aldh1a3 56847 NM_053080.2 0.885 1.355 2.149 ILMN_2643534 Angptl6 70726 NM_145154 0.662 0.629 0.454 ILMN_2718030 Ank2 109676 NM_001034168.1 0.639 0.757 0.457 ILMN_2950286 Ankrd1 107765 NM_013468.2 1.216 1.523 1.516 ILMN_3103575 Ankrd6 140577 NM_001012451.1 0.549 0.797 0.379 ILMN_2625920 Aoc3 11754 NM_009675.1 0.935 1.091 2.136 ILMN_2888834 Apob48r 171504 NM_138310.1 0.624 0.703 0.576 ILMN_3115472 Aqp5 11830 NM_009701.4 3.127 1.052 4.378 ILMN_1241458 Arap1 69710 NM_001040112.1 0.594 0.806 0.413 ILMN_2952275 Arg1 11846 NM_007482.2 2.471 1.433 3.998 ILMN_2950622 Arhgdig 14570 NM_008113.3 0.929 0.826 0.628 ILMN_2636755 Asns 27053 NM_012055.3 0.557 0.587 0.509 ILMN_2767615 Atp1b1 11931 NM_009721.4 1.938 1.516 1.957 ILMN_2666225 Atp5sl 66349 NM_025504.4 1.380 1.125 1.686 ILMN_2977129 Atp8b1 54670 NM_001001488.3 0.456 0.707 0.539 ILMN_2603662 B230312A22Rik 230088 NM_172691.2 1.288 1.374 1.527 ILMN_1216368 B3gnt5 108105 NM_054052.2 1.303 1.190 1.512 ILMN_2665609 Baiap2l1 66898 NM_025833.3 1.695 1.546 2.306 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION Gadd45a -/- Ing1 -/- DKO

ILMN_1226639 BC006779 229003 XM_485132 0.648 0.813 0.528 ILMN_2436183 Bcl11b 58208 NM_021399.2 0.859 0.806 0.548 ILMN_3105417 Bdnf 12064 NM_001048141.1 1.592 1.287 1.763 ILMN_2939138 Bicc1 83675 NM_031397.2 0.750 0.851 0.613 ILMN_1236010 Bicc1 83675 AK076154.1 0.732 0.773 0.602 ILMN_1215252 Bmp4 12159 NM_007554.2 4.482 3.282 3.636 ILMN_1216262 Bmpr1b 12167 NM_007560.3 1.081 1.281 1.592 ILMN_1222934 Bves 23828 NM_024285 1.997 0.949 1.680 ILMN_1239464 C030027H14Rik 77465 - 1.634 1.195 1.532 ILMN_2603249 C130021I20Rik 100504399 NM_177842.2 2.403 2.055 3.571 ILMN_2619620 C1qb 12260 NM_009777.2 4.371 3.586 1.234 ILMN_2715840 C1qc 12262 NM_007574.2 2.971 2.850 0.931 ILMN_1232458 C1qtnf2 69183 NM_026979.3 0.882 0.942 0.585 ILMN_2863849 C1qtnf3 81799 NM_030888.2 1.721 1.118 1.908 ILMN_2593034 C1qtnf3 81799 NM_030888.3 1.600 0.991 1.848 ILMN_2612895 C2 12263 NM_013484.1 0.673 0.305 0.332 ILMN_1238039 C230060E24 329496 XM_488955 1.495 1.157 1.993 ILMN_1241838 Cacna1g 12291 NM_009783.1 0.527 0.768 0.492 ILMN_2695143 Capn6 12338 NM_007603.2 1.087 0.508 0.868 ILMN_2811737 Casp4 12363 NM_007609.1 0.304 0.485 0.218 ILMN_2756665 Cbr2 12409 NM_007621.1 6.569 2.186 4.613 ILMN_2629052 Cbx3 12417 NM_007624 0.508 0.767 0.492 ILMN_2929572 Ccdc68 381175 NM_201362.1 2.611 2.364 2.934 ILMN_2649550 Ccdc85b 240514 NM_198616.2 1.461 1.178 1.641 ILMN_1252990 Cck 12424 NM_031161.2 3.406 0.979 4.552 ILMN_2647757 Ccl11 20292 NM_011330.2 0.390 0.498 0.275 ILMN_2717015 Ccl17 20295 NM_011332.2 2.082 0.982 3.491 ILMN_2771176 Ccl7 20306 NM_013654 0.659 0.826 0.679 ILMN_2835117 Ccl7 20306 NM_013654.2 0.562 0.739 0.663 ILMN_3115796 Cd40 21939 NM_170702.2 0.608 1.318 0.534 ILMN_2502136 Cd40 21939 NM_170702.2 0.664 1.390 0.508 ILMN_2910934 Cd52 23833 NM_013706.1 4.504 2.994 1.791 ILMN_1228942 Cd59a 12509 NM_007652.2 0.645 1.143 0.517 ILMN_3156246 Cdh3 12560 NM_001037809.1 0.710 0.819 0.543 ILMN_2846775 Cdkn1a 12575 NM_007669.2 1.257 1.141 1.679 ILMN_2426115 Cflar 12633 - 1.274 1.401 1.605 ILMN_2736038 Cgnl1 68178 NM_026599.3 1.573 1.102 1.734 ILMN_2617468 Chac1 69065 NM_026929.3 0.638 0.717 0.581 ILMN_2749037 Chchd10 103172 NM_175329.3 0.371 0.624 0.325 ILMN_1255385 Chst1 76969 NM_023850.1 1.722 1.158 1.910 ILMN_1239627 Chst15 77590 NM_029935.4 0.735 0.777 0.511 ILMN_2428931 Chst15 77590 NM_029935 0.635 0.810 0.313 ILMN_2687165 Chst2 54371 NM_018763.1 1.051 1.669 1.179 ILMN_1216374 Chst7 60322 NM_021715.1 3.483 1.822 4.024 ILMN_2683980 Cited2 17684 NM_010828.2 1.740 1.408 1.641 ILMN_2870295 Cldn1 12737 NM_016674.2 0.444 0.545 0.274 ILMN_2603647 Clec2d 93694 NM_053109.2 0.853 0.794 0.591 ILMN_2782634 Cobll1 319876 NM_177025.3 1.746 1.172 1.761 ILMN_1222111 Col15a1 12819 NM_009928.3 0.716 0.735 0.526 ILMN_2857666 Col24a1 71355 NM_027770.2 0.550 0.417 0.267 ILMN_1231275 Col24a1 71355 NM_027770.2 0.563 0.536 0.253 ILMN_1246054 Col2a1 12824 NM_031163.2 16.087 2.744 9.100 ILMN_2759142 Col2a1 12824 NM_031163.2 10.130 1.853 6.283 ILMN_2759144 Col2a1 12824 NM_031163 12.768 2.108 8.013 ILMN_2768087 Col6a1 12833 NM_009933.2 0.748 0.946 0.619 ILMN_1216661 Col6a2 12834 NM_146007.1 0.774 0.843 0.563 ILMN_1233848 Copg 54161 NM_201244.1 1.344 1.607 1.698 ILMN_2629581 Cox6a2 12862 NM_009943.2 0.383 0.496 0.196 ILMN_3007758 Creb5 231991 NM_172728.1 1.812 1.381 1.946 ILMN_2525274 Crim1 50766 XM_128751 1.074 1.207 1.789 ILMN_2710449 Crip2 68337 NM_024223.1 1.816 1.341 1.579 ILMN_1257551 Crispld2 78892 NM_030209.2 0.818 0.889 0.623 ILMN_2747811 Crlf1 12931 NM_018827.2 1.562 1.247 1.964 ILMN_2702444 Csgalnact1 234356 NM_172753.3 0.468 0.668 0.522 ILMN_3145415 Cstf3 228410 NM_177253.1 1.336 1.330 1.697 ILMN_3008859 Ctsc 13032 NM_009982.2 0.712 0.577 0.479 ILMN_1238486 Ctsc 13032 NM_009982.3 0.757 0.482 0.556 ILMN_1222071 Ctse 13034 - 0.435 0.868 0.764 ILMN_2872058 Ctsh 13036 NM_007801.1 1.161 1.357 1.782 ILMN_2775154 Ctsh 13036 NM_007801 1.129 1.391 1.872 ILMN_2711163 Ctsk 13038 NM_007802.3 0.605 0.804 0.566 ILMN_3018017 Cxadr 13052 NM_001025192.2 0.586 0.615 0.397 ILMN_2514377 Cxadr 13052 NM_009988 0.468 0.472 0.244 ILMN_2763245 Cxcl1 14825 NM_008176.1 0.578 0.516 0.380 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION Gadd45a -/- Ing1 -/- DKO

ILMN_2760800 Cxcl14 57266 NM_019568.2 0.832 0.569 0.542 ILMN_1243370 Cyb5r1 72017 NM_028057.2 0.515 0.635 0.715 ILMN_1254109 Cyp4a12a 277753 NM_177406.3 0.896 0.885 0.480 ILMN_2680054 D0H4S114 27528 NM_053078.3 0.467 0.782 0.476 ILMN_2707694 D10Wsu102e 28109 NM_026579.2 1.885 1.903 1.956 ILMN_2693858 D14Ertd449e 66039 NM_025311.1 2.176 1.535 2.958 ILMN_1234812 Dap 223453 NM_146057.1 1.387 1.105 1.615 ILMN_2472606 Dbc1 56710 NM_019967.2 1.127 1.074 1.513 ILMN_2747959 Dcn 13179 NM_007833.4 0.539 0.637 0.292 ILMN_2596346 Dcn 13179 NM_007833.4 0.437 0.490 0.257 ILMN_2695819 Ddit4l 73284 NM_030143.3 1.760 1.216 1.770 ILMN_2836982 Des 13346 NM_010043.1 1.122 1.023 1.656 ILMN_2652482 Dfna5h 54722 NM_018769.3 0.301 0.874 0.354 ILMN_2660471 Dhcr7 13360 NM_007856.2 0.757 0.962 0.600 ILMN_1244618 Dlk1 13386 NM_010052.4 2.230 1.442 1.551 ILMN_2699621 Dlk2 106565 NM_207666.2 1.949 1.463 2.016 ILMN_2860959 Dlx2 13392 NM_010054.1 3.849 1.872 4.716 ILMN_1237061 Dmpk 13400 NM_032418 2.419 1.433 4.354 ILMN_1243949 Dner 227325 NM_152915.1 1.855 2.256 3.069 ILMN_1250149 Dnmt3l 54427 NM_001081695.1 0.439 0.377 0.296 ILMN_2606210 Dpt 56429 NM_019759.2 0.590 0.854 0.409 ILMN_1220813 Dtx3l 209200 NM_001013371.2 0.722 0.621 0.427 ILMN_2450767 Dusp4 319520 NM_176933 1.107 1.255 1.513 ILMN_2870965 Dusp4 319520 NM_176933.3 1.128 1.358 1.616 ILMN_2531737 Dusp5 240672 XM_140740.3 1.441 1.405 1.784 ILMN_2699522 Dyrk3 226419 NM_145508.2 1.691 1.522 1.892 ILMN_2420956 Dysf 26903 NM_021469.2 1.249 1.094 1.672 ILMN_2674351 Ednra 13617 NM_010332.2 0.724 0.856 0.600 ILMN_2588130 EG630499 630499 NM_001081015.1 0.937 0.852 0.607 ILMN_2977390 EG633640 633640 NM_001039244.1 0.305 1.742 2.460 ILMN_1250507 Elovl4 83603 NM_148941.1 1.198 1.179 1.656 ILMN_1259365 Emcn 59308 NM_016885.1 2.136 3.198 3.568 ILMN_2757569 Eno3 13808 NM_007933.2 1.645 1.020 1.580 ILMN_2749695 Enox1 239188 NM_172813.2 0.729 0.829 0.147 ILMN_1231851 Enpp1 18605 NM_008813.3 1.903 1.325 1.747 ILMN_2554110 Entpd4 67464 NM_026174.2 1.000 8.523 6.927 ILMN_2688653 Epha2 13836 NM_010139.2 1.553 0.849 1.966 ILMN_2629804 Epha3 13837 NM_010140.1 0.723 0.703 0.556 ILMN_2831656 Epha3 13837 NM_010140.1 0.836 0.753 0.586 ILMN_2629805 Epha3 13837 NM_010140.3 0.712 0.662 0.644 ILMN_1246153 Erdr1 170942 NM_133362.2 12.914 26.935 16.644 ILMN_2998658 Erdr1 170942 NM_133362.1 1.000 150.958 1.000 ILMN_1257574 Esm1 71690 NM_023612.3 1.788 1.442 4.719 ILMN_1259022 Etl4 208618 NM_001081006.1 1.015 1.073 0.511 ILMN_2877280 Exosc5 27998 NM_138586.1 0.979 0.861 0.663 ILMN_2769567 F2rl1 14063 NM_007974 0.649 1.049 0.539 ILMN_2866267 F2rl1 14063 NM_007974.2 0.722 1.232 0.520 ILMN_2887630 Fabp3 14077 NM_010174.1 1.455 1.174 1.891 ILMN_2519802 Fads2 56473 NM_019699 0.705 1.001 0.626 ILMN_2591031 Fam129a 63913 NM_022018.2 0.735 0.725 0.657 ILMN_2591158 Fam13c 71721 NM_024244 0.712 0.577 0.548 ILMN_2591159 Fam13c 71721 NM_024244.3 0.568 0.550 0.452 ILMN_3014674 Fam169b 434197 NM_001013811.2 0.550 0.682 0.194 ILMN_1218877 Fam20a 208659 NM_153782.1 0.634 0.620 0.626 ILMN_2431483 Fam65b 193385 XM_484234 1.605 1.377 1.794 ILMN_2870672 Fbln1 14114 NM_010180.1 0.782 0.827 0.612 ILMN_2449644 Fbln1 14114 NM_010180 0.694 0.811 0.622 ILMN_2748875 Fcer1g 14127 NM_010185.2 2.145 1.632 1.042 ILMN_2770968 Fcrls 80891 NM_030707.3 4.786 4.762 0.726 ILMN_2982771 Fgf10 14165 NM_008002.3 1.709 0.962 0.736 ILMN_2736497 Fgf10 14165 NM_008002.3 1.624 1.021 0.871 ILMN_2745480 Fgf13 14168 NM_010200.2 1.430 1.180 1.602 ILMN_2710698 Fgf21 56636 NM_020013.4 0.339 0.516 0.146 ILMN_2935157 Fkhl18 14239 NM_010226.1 1.225 1.330 1.873 ILMN_2495167 Flrt1 396184 - 1.791 0.798 1.681 ILMN_1227926 Flt1 14254 NM_010228.3 0.783 1.031 0.551 ILMN_2886260 Foxc1 17300 NM_008592.2 3.508 1.766 2.433 ILMN_2703433 Foxc2 14234 NM_013519.1 1.341 1.067 2.270 ILMN_2599125 Foxg1 15228 NM_008241.1 5.613 2.533 6.457 ILMN_1228958 Fst 14313 NM_008046.2 2.202 1.130 1.622 ILMN_1249466 Fut10 171167 NM_001012517.4 1.020 0.366 0.352 ILMN_2665035 Fut10 171167 NM_134161.2 0.910 0.102 0.173 ILMN_3011294 Fut10 171167 NM_001012517.2 0.992 0.512 0.428 ILMN_2967266 Fxyd5 18301 NM_008761.2 1.652 1.219 1.413 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION Gadd45a -/- Ing1 -/- DKO

ILMN_2609998 Fxyd6 59095 NM_022004.6 0.695 0.677 0.439 ILMN_2476948 Gabrb3 14402 NM_001038701.1 1.999 1.666 1.209 ILMN_2742152 Gadd45a 13197 NM_007836.1 2.014 0.608 1.902 ILMN_2736514 Galntl4 233733 NM_173739.3 1.179 1.771 1.533 ILMN_1234990 Gap43 14432 NM_008083.2 0.998 0.420 0.365 ILMN_1235488 Garnl3 99326 NM_178888.4 1.219 1.583 1.546 ILMN_2612283 Gata2 14461 NM_008090.4 1.740 1.092 2.528 ILMN_3122961 Gbp2 14469 NM_010260.1 0.820 0.588 0.550 ILMN_2735350 Gdf15 23886 NM_011819.1 1.594 1.240 2.356 ILMN_2859032 Gfod1 328232 NM_001033399.1 1.235 1.563 1.640 ILMN_2798138 Gipc2 54120 NM_016867.1 2.238 1.256 3.520 ILMN_1244291 Gja1 14609 NM_010288.2 1.509 1.295 1.546 ILMN_2999627 Gjb2 14619 NM_008125.2 1.551 1.024 1.615 ILMN_1227148 Gjb2 14619 NM_008125.2 1.303 0.906 1.860 ILMN_2879102 Gjb3 14620 NM_008126.1 2.042 0.917 3.580 ILMN_2522863 Gli2 14633 NM_001081125.1 0.934 0.775 0.620 ILMN_1238174 Glis3 226075 - 1.463 0.783 1.503 ILMN_2592815 Gnai1 14677 NM_010305.1 1.714 1.270 1.623 ILMN_2747135 Gper 76854 NM_029771.2 2.896 1.948 1.634 ILMN_2648669 Gpnmb 93695 NM_053110.3 0.760 0.742 0.635 ILMN_2856926 Gpr114 382045 NM_001033468.1 2.971 2.859 4.561 ILMN_1246785 Gprc5a 232431 NM_181444 1.807 1.603 2.095 ILMN_2854943 Gprc5a 232431 NM_181444.3 1.900 1.473 2.080 ILMN_1234702 Gpt2 108682 NM_173866.3 0.691 0.676 0.560 ILMN_2610565 Grem2 23893 NM_011825.1 1.045 0.972 1.512 ILMN_2432568 Grid2 14804 NM_008167 10.965 1.208 10.087 ILMN_2513378 Grin3a 242443 - 2.966 1.802 3.626 ILMN_2941324 Gsdmdc1 69146 NM_026960.1 0.656 0.629 0.547 ILMN_2892441 Gsta4 14860 NM_010357.1 2.211 0.750 2.444 ILMN_2476267 H2-D1 14964 NM_010380.3 0.819 0.685 0.603 ILMN_2462745 H2-D1 14964 NM_010380.3 0.903 0.771 0.621 ILMN_2862706 H2-Q5 15016 NM_010393.1 0.756 0.904 0.560 ILMN_1230878 H2-T10 15024 NM_010395.5 0.766 0.679 0.513 ILMN_2777474 H2-T23 15040 NM_010398.1 0.687 0.698 0.519 ILMN_2777471 H2-T23 15040 NM_010398.1 0.621 0.756 0.522 ILMN_1223179 H2-T23 15040 NM_010398.3 0.716 0.597 0.505 ILMN_1254975 Has2 15117 NM_008216.2 1.502 1.186 1.783 ILMN_2698449 Hbegf 15200 NM_010415.1 1.633 1.463 2.020 ILMN_2690596 Hey1 15213 NM_010423.2 1.499 1.156 1.759 ILMN_2664129 Hist1h4h 69386 NM_153173.2 1.747 1.539 1.902 ILMN_2637757 Hlx 15284 NM_008250.1 2.344 1.571 1.907 ILMN_2521893 Hmga2-ps1 15365 BC064076.1 2.031 1.759 1.999 ILMN_2619975 Hoxa11as 15397 XM_149724.5 1.121 1.619 3.885 ILMN_1217978 Hoxa5 15402 NM_010453.2 1.854 1.934 1.956 ILMN_2621038 Hoxa7 15404 NM_010455.2 1.820 1.848 1.716 ILMN_2693052 Hoxd8 15437 NM_008276.2 0.672 0.665 0.488 ILMN_3158500 Hs6st1 50785 NM_015818.1 0.609 0.722 0.551 ILMN_1260456 Hsd3b7 101502 NM_133943.2 0.784 0.555 0.548 ILMN_2706269 Hspb1 15507 NM_013560.1 1.215 1.120 1.562 ILMN_2805339 Hspb6 243912 NM_001012401.1 1.574 1.022 1.621 ILMN_2746738 Htra1 56213 NM_019564.2 0.497 0.830 0.641 ILMN_2966104 Htra1 56213 NM_019564.1 0.457 0.786 0.658 ILMN_1243451 Hvcn1 74096 NM_001042489.1 0.601 0.458 0.232 ILMN_2672190 Id1 15901 NM_010495.2 1.935 1.180 2.518 ILMN_1228557 Id2 15902 NM_010496.2 1.493 0.821 2.207 ILMN_1238102 Ide 15925 AK029089 1.360 3.578 3.318 ILMN_1214071 Ifitm1 68713 NM_026820.2 0.426 0.862 0.517 ILMN_1219335 Igfbp3 16009 NM_008343.2 0.466 0.272 0.248 ILMN_1244809 Igsf10 242050 XM_913941.2 0.636 0.739 0.363 ILMN_2674966 Igsf10 242050 XM_143254 0.723 0.832 0.442 ILMN_1259564 Iigp2 54396 NM_019440.2 0.930 0.691 0.212 ILMN_1243862 Il11 16156 NM_008350.2 2.029 0.975 2.778 ILMN_1248657 Il17rd 171463 NM_134437.3 0.521 0.595 0.453 ILMN_3072427 Il1rn 16181 NM_031167.3 9.114 1.169 4.469 ILMN_2621752 Irf5 27056 NM_012057.3 1.270 0.835 2.190 ILMN_1233461 Irf9 16391 NM_008394.2 0.708 0.604 0.482 ILMN_2717099 Irx2 16372 NM_010574 0.737 0.819 0.608 ILMN_3115213 Irx2 16372 NM_010574.2 0.842 0.926 0.611 ILMN_2636424 Itgbl1 223272 NM_145467.1 0.379 0.459 0.209 ILMN_2592881 Jam2 67374 NM_023844.4 2.248 3.114 6.726 ILMN_2438153 Jph2 59091 BC022635.1 1.660 1.175 1.892 ILMN_1256894 Kcne4 57814 NM_021342.1 0.606 0.515 0.359 ILMN_1258376 Kcnk6 52150 NM_001033525.2 1.677 1.009 1.015 ILMN_2835384 Kif26b 269152 NM_177757.3 0.597 0.696 0.642 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION Gadd45a -/- Ing1 -/- DKO

ILMN_1216662 Kif5c 16574 NM_008449.2 1.776 1.017 1.910 ILMN_2604029 Klf2 16598 NM_008452.1 1.583 1.189 1.573 ILMN_2513451 Klhl24 75785 - 0.666 0.817 0.625 ILMN_2675232 Klk8 259277 NM_008940.2 1.959 1.422 1.401 ILMN_2614462 Krt19 16669 NM_008471.2 2.543 2.206 3.447 ILMN_1217849 Laptm5 16792 NM_010686.3 1.760 1.576 0.906 ILMN_2593523 Lce1f 67828 NM_026394.2 2.072 2.615 4.155 ILMN_3112526 Ldb2 16826 NM_001077398.1 0.478 0.804 0.326 ILMN_2754435 Ldb2 16826 NM_010698.2 0.563 0.866 0.429 ILMN_1258526 Lgals3bp 19039 NM_011150.2 0.631 0.633 0.539 ILMN_2650008 Lgr5 14160 NM_010195.2 0.933 0.881 0.634 ILMN_3160067 Lhx9 16876 NM_001025565.2 6.479 2.213 3.945 ILMN_2628603 Limch1 77569 NM_001001980.2 2.021 0.957 1.585 ILMN_1247343 Lmcd1 30937 NM_144799.1 0.752 0.274 0.577 ILMN_1256257 LOC100038882 100038882 XM_001471686.1 0.576 0.572 0.356 ILMN_1248616 LOC100038993 100038993 NM_001100596.1 0.928 0.979 0.333 ILMN_1225825 LOC100039175 100039175 XM_001472394.1 2.608 1.401 2.641 ILMN_2654952 LOC100040592 100040592 XM_001475189.1 0.852 0.927 0.660 ILMN_2455771 LOC100044411 100044411 XM_001472216.1 2.247 1.165 1.718 ILMN_1231651 LOC100045439 100045439 XM_001474279.1 0.665 0.858 0.478 ILMN_2607529 LOC100046044 100046044 XM_001475459.1 0.558 0.538 0.777 ILMN_2653725 LOC100046802 100046802 XM_001476835.1 0.643 0.728 0.603 ILMN_2739156 LOC100047260 100047260 XM_001477752.1 0.668 0.846 0.633 ILMN_2668927 LOC100047583 100047583 XM_001479138.1 0.372 0.644 0.233 ILMN_1255207 LOC100047749 100047749 XM_001478817.1 0.605 0.579 0.676 ILMN_1242935 LOC633016 633016 XM_921371.2 0.634 0.930 0.530 ILMN_1239601 LOC637711 637711 XM_913466.2 0.860 1.030 0.653 ILMN_1257771 LOC638301 638301 XM_914287.2 0.616 0.671 0.588 ILMN_1224237 LOC641366 641366 XM_981039.1 0.797 0.837 0.539 ILMN_2481836 LOC668047 668047 XM_001001100.1 0.837 3.623 1.923 ILMN_1213448 LOC669658 669658 XM_976371.1 0.304 1.009 0.334 ILMN_2732816 LOC674135 674135 XR_004604.2 0.847 0.769 0.580 ILMN_1259641 LOC674912 674912 XM_979860.1 0.862 0.790 0.557 ILMN_1241825 Lor 16939 NM_008508.2 2.409 1.944 2.700 ILMN_3111744 Lpin1 14245 NM_172950.2 0.733 0.810 0.443 ILMN_2756421 Lrrc15 74488 XM_358823.1 0.771 1.074 0.607 ILMN_2511456 Lrrc17 74511 XM_904948.2 0.843 0.891 0.606 ILMN_2773259 Lum 17022 NM_008524 0.182 0.316 0.175 ILMN_3001540 Lum 17022 NM_008524.1 0.305 0.252 0.112 ILMN_2878071 Lyz 17110 NM_013590.2 1.639 1.171 0.795 ILMN_1252076 Lyz2 17105 NM_017372.3 1.803 1.154 0.769 ILMN_1250116 Masp1 17174 AK031598.1 1.435 1.017 2.181 ILMN_1250760 Masp1 17174 AK043055 1.478 0.622 2.579 ILMN_1225029 Mboat1 218121 NM_153546.3 1.669 0.831 1.189 ILMN_2689784 Mcf2l 17207 NM_178076.2 2.378 1.656 3.083 ILMN_2847276 Mcf2l 17207 NM_178076.2 2.712 1.216 2.917 ILMN_1251193 Med23 70208 AK042346 0.542 0.796 0.679 ILMN_1213886 Meox1 17285 NM_010791.3 1.187 2.426 2.278 ILMN_2642417 Mest 17294 NM_008590.1 1.177 1.237 0.445 ILMN_2846904 Mest 17294 NM_008590.1 0.927 0.991 0.580 ILMN_2642418 Mest 17294 NM_008590.1 1.086 1.111 0.513 ILMN_2633350 Mfap4 76293 NM_029568.2 0.555 0.683 0.260 ILMN_1247765 Mfhas1 52065 NM_001081279.1 0.749 0.789 0.521 ILMN_2432103 Mfhas1 52065 NM_001081279.1 0.777 0.614 0.233 ILMN_2700408 Mgll 23945 NM_011844.3 0.676 0.947 0.582 ILMN_1232183 Mgmt 17314 NM_008598.1 1.369 1.276 1.705 ILMN_2876448 Mgmt 17314 NM_008598.2 1.640 1.421 2.080 ILMN_2666018 Mgp 17313 NM_008597.3 3.358 2.061 2.371 ILMN_2615035 Mgst3 66447 NM_025569.1 1.740 1.286 1.188 ILMN_3159435 Mid1 17318 NM_183151.1 6.136 1.421 3.019 ILMN_2619452 Mid1 17318 NM_010797.1 8.140 2.326 3.005 ILMN_3006767 Mlkl 74568 NM_029005.1 0.627 0.510 0.515 ILMN_2674575 Mmd 67468 NM_026178.2 1.157 1.201 1.562 ILMN_2696711 Mmp11 17385 NM_008606.2 0.693 0.710 0.525 ILMN_2737685 Mmp13 17386 NM_008607.1 0.364 0.416 0.181 ILMN_2980226 Mmp16 17389 NM_019724.2 1.926 1.386 1.283 ILMN_2753809 Mmp3 17392 NM_010809.1 0.662 2.175 3.891 ILMN_2899041 Mmp3 17392 NM_010809.1 0.397 1.294 2.058 ILMN_2711075 Mmp9 17395 NM_013599.2 0.438 0.872 0.425 ILMN_2977492 Moxd1 59012 NM_021509.3 0.385 0.436 0.296 ILMN_2760254 Mrgprf 211577 NM_145379.2 0.740 0.805 0.450 ILMN_2746283 Mrvi1 17540 NM_194464.2 0.993 1.200 1.660 ILMN_1246173 Msx1 17701 NM_010835.2 0.300 0.392 0.407 ILMN_2596522 Mt1 17748 NM_013602.2 0.734 0.743 0.664 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION Gadd45a -/- Ing1 -/- DKO

ILMN_2439378 Mtap6 17760 NM_001048167.1 1.576 1.367 1.768 ILMN_2497745 Mtap9 213582 NM_001081230.1 1.340 1.609 1.670 ILMN_3142257 Mtus1 102103 NM_001005864.2 0.782 0.898 0.637 ILMN_2658461 Mustn1 66175 NM_181390.2 3.241 1.258 2.975 ILMN_2797928 Mustn1 66175 NM_181390.1 3.048 1.299 2.234 ILMN_2622217 Myh11 17880 NM_013607.1 2.083 1.351 2.089 ILMN_1219471 Mylk 107589 NM_139300.3 2.121 1.890 3.316 ILMN_1218347 Mylk 107589 NM_139300.3 1.516 1.647 2.631 ILMN_2662602 Mylk 107589 NM_139300.3 1.868 1.692 2.816 ILMN_2506244 Mylk2 228785 XM_130630 1.279 1.183 1.866 ILMN_2506245 Mylk2 228785 NM_001081044.1 1.316 1.313 1.688 ILMN_2435360 Myocd 214384 NM_145136.4 2.317 1.949 3.127 ILMN_2815138 Myom1 17929 NM_010867.1 1.717 1.548 2.006 ILMN_2777478 Nbl1 17965 NM_008675.2 0.988 1.165 1.529 ILMN_2646166 Ndrg1 17988 NM_008681 0.729 0.706 0.567 ILMN_1250195 Ndrg1 17988 NM_008681.2 0.687 0.806 0.556 ILMN_2551723 Ndufaf4 68493 AK019042 1.444 1.375 1.588 ILMN_1252297 Nek3 23954 NM_011848.2 1.359 3.183 1.962 ILMN_2703267 Nes 18008 NM_016701.3 1.426 1.484 1.827 ILMN_2904590 Nes 18008 NM_016701.3 1.452 1.510 1.745 ILMN_2625940 Neurl1a 18011 NM_021360 0.816 0.822 0.634 ILMN_2726585 Nfib 18028 NM_008687.2 0.966 0.778 0.635 ILMN_2646631 Nfib 18028 NM_175553 0.978 0.821 0.639 ILMN_1241756 Nfib 18028 NM_175553 0.876 0.761 0.659 ILMN_2937596 Ngfb 18049 NM_013609.1 2.610 2.093 4.181 ILMN_2660233 Ngfb 18049 NM_013609.1 2.555 2.004 4.079 ILMN_2420209 Nhsl2 100042480 - 0.468 0.636 0.343 ILMN_2476742 Nhsl2 100042480 - 0.466 0.644 0.354 ILMN_2510694 Nme7 171567 NM_138314.2 1.552 1.225 2.180 ILMN_1259075 Nme7 171567 NM_138314.2 1.720 1.282 1.696 ILMN_1214703 Nme7 171567 NM_138314.2 1.463 1.131 2.098 ILMN_1247710 Nod1 107607 NM_172729.2 0.719 0.770 0.467 ILMN_2752454 Npal1 70701 NM_001081205.1 1.454 1.281 1.585 ILMN_3127391 Npr3 18162 NM_008728.2 0.978 1.213 2.120 ILMN_1236914 Npr3 18162 NM_001039181.1 1.612 2.315 3.467 ILMN_2604333 Npr3 18162 NM_008728 0.995 1.292 1.920 ILMN_2620406 Nptx2 53324 NM_016789.2 1.881 1.153 1.829 ILMN_2726371 Nqo1 18104 NM_008706.4 1.408 0.762 1.525 ILMN_2699052 Nrn1 68404 NM_153529.1 1.893 1.301 2.781 ILMN_2603081 Nt5c3 107569 NM_026004.2 0.331 0.959 0.359 ILMN_2680038 Nuak2 74137 NM_028778.3 1.226 1.348 1.594 ILMN_2954868 Oasl2 23962 NM_011854.1 0.492 0.683 0.412 ILMN_2741231 Odz3 23965 NM_011857.2 0.861 0.755 0.506 ILMN_1231794 Odz3 23965 NM_011857.2 0.539 0.675 0.344 ILMN_1230926 Odz4 23966 NM_011858.3 0.491 0.728 0.181 ILMN_3162820 Odz4 23966 NM_011858.3 0.528 0.969 0.149 ILMN_1233455 Olfml3 99543 NM_133859.2 0.841 0.861 0.649 ILMN_2781784 Osr2 107587 NM_054049.1 0.480 0.805 0.587 ILMN_1245081 Otud4 73945 NM_001081164.1 1.203 1.048 1.608 ILMN_2772717 P2rx3 228139 NM_145526.2 0.255 0.255 0.255 ILMN_2825803 Parp14 547253 NM_001039530.1 0.548 0.500 0.201 ILMN_2640457 Pcdhb22 93893 NM_053147.3 0.535 0.750 0.570 ILMN_1254622 Pcp4l1 66425 XM_484933.5 3.517 2.102 3.531 ILMN_2756023 Pcsk9 100102 NM_153565.1 0.643 0.875 0.404 ILMN_3132186 Pcyt1b 236899 NM_177546.2 0.666 0.851 0.554 ILMN_2730293 Pde1b 18574 NM_008800 1.153 1.157 1.807 ILMN_3064283 Pde4dip 83679 NM_001039376.1 4.141 4.348 5.819 ILMN_2424721 Pdgfa 18590 NM_008808 1.233 1.080 1.666 ILMN_1235932 Pdgfra 18595 NM_011058.2 0.712 0.697 0.421 ILMN_1259322 Pdk4 27273 NM_013743.2 1.481 1.592 3.864 ILMN_2619767 Pdlim2 213019 NM_145978.1 0.774 0.911 0.616 ILMN_2880906 Pdlim2 213019 NM_145978.1 0.675 0.758 0.602 ILMN_2768533 Pgf 18654 NM_008827.2 3.506 3.260 4.459 ILMN_2846254 Pgpep1 66522 NM_023217.2 1.244 1.400 1.715 ILMN_2754985 Phlda1 21664 NM_009344.1 1.437 1.184 1.813 ILMN_2680549 Pik3cb 74769 NM_029094.1 1.444 0.973 1.601 ILMN_2762109 Pkp1 18772 NM_019645.2 2.621 1.237 4.062 ILMN_2710159 Plac9 211623 NM_207229 3.031 1.412 3.162 ILMN_2775937 Plat 18791 NM_008872 0.831 0.837 0.598 ILMN_2590884 Plaur 18793 NM_011113.3 1.418 1.201 1.604 ILMN_2770429 Plod2 26432 NM_011961 1.289 1.385 1.682 ILMN_2772936 Polr2h 245841 NM_145632.2 1.400 1.096 1.512 ILMN_1222991 Ppap2a 19012 NM_008903.1 1.187 0.735 1.574 ILMN_2759079 Ppap2a 19012 NM_008247.2 1.325 0.962 1.560 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION Gadd45a -/- Ing1 -/- DKO

ILMN_1258830 Ppap2a 19012 NM_008247.2 1.453 0.899 1.560 ILMN_1221060 Pparg 19016 NM_011146.2 1.390 0.834 1.978 ILMN_2967455 Ppp1r13b 21981 NM_011625.1 0.867 1.018 0.637 ILMN_2616584 Ppp1r1a 58200 NM_021391.3 1.767 1.373 2.380 ILMN_1255611 Ppp1r3d 228966 - 0.777 1.028 0.483 ILMN_2739760 Prelp 116847 NM_054077.3 1.114 0.551 0.570 ILMN_1228245 Prickle1 106042 NM_001033217.3 0.848 0.859 0.616 ILMN_2734036 Prrx2 20204 XM_149096.1 1.870 1.049 2.262 ILMN_2609897 Prss35 244954 NM_178738.2 1.808 2.186 1.457 ILMN_2638114 Ptn 19242 NM_008973.2 0.831 0.758 0.565 ILMN_2662802 Ptx3 19288 NM_008987.2 1.110 0.566 0.896 ILMN_2972585 Pvr 52118 NM_027514.1 1.189 1.003 1.651 ILMN_1258275 Pvr 52118 AK014446 1.345 1.195 1.746 ILMN_2627296 Pvr 52118 NM_027514.1 1.293 1.079 1.598 ILMN_2588737 Rab3d 19340 NM_031874.4 0.859 0.893 0.573 ILMN_2483811 Ralgps2 78255 - 0.690 0.593 0.350 ILMN_1247585 Ralgps2 78255 NM_023884 0.504 0.651 0.406 ILMN_2884869 Ralgps2 78255 NM_023884.2 0.750 0.860 0.456 ILMN_2749052 Ramp3 56089 NM_019511.3 0.804 0.438 0.511 ILMN_1233634 Rasal2 226525 NM_177644.4 1.383 1.198 1.899 ILMN_2908687 Rasgrp3 240168 NM_207246.2 2.026 1.305 2.039 ILMN_2513570 Rassf8 71323 - 0.617 0.749 0.652 ILMN_1238309 Rbfox1 268859 NM_021477.2 1.760 1.521 3.380 ILMN_3009910 Rbm13 67920 NM_026453.1 1.224 0.018 0.045 ILMN_1220508 Rbm20 73713 XM_140742.4 0.273 0.457 0.467 ILMN_1238433 Rbp1 19659 NM_011254.2 0.649 0.644 0.574 ILMN_3026557 Rbpms 19663 NM_001042675.1 0.916 1.596 1.709 ILMN_3106592 Rcan2 53901 NM_207649.1 1.737 1.099 1.615 ILMN_1228010 Rem1 19700 NM_009047.5 1.576 1.149 2.302 ILMN_1230648 Rerg 232441 NM_181988.1 0.739 0.807 0.435 ILMN_1214500 Rgma 244058 NM_177740.4 0.630 0.793 0.401 ILMN_1244081 Rgs4 19736 NM_009062.3 1.878 1.222 1.878 ILMN_2634970 Ripk2 192656 NM_138952.3 1.679 1.153 2.171 ILMN_1229455 Rnf213 629974 NM_001040005.2 0.925 0.917 0.637 ILMN_1243741 Rora 19883 NM_013646.1 0.782 0.627 0.494 ILMN_1227403 Rtn4rl1 237847 NM_177708.5 0.806 0.754 0.468 ILMN_2987984 S100a13 20196 NM_009113.3 1.342 1.115 1.558 ILMN_1224855 Samd9l 209086 XM_620286.3 0.716 0.717 0.548 ILMN_2919259 Scd2 20250 NM_009128.1 0.746 0.869 0.662 ILMN_1226016 Scx 20289 NM_198885.2 1.815 0.749 2.471 ILMN_2728729 Sdc4 20971 NM_011521.2 1.742 1.310 1.629 ILMN_2635631 Sema3f 20350 NM_011349.2 0.801 0.617 0.471 ILMN_1248740 Sema3f 20350 NM_011349.3 0.752 0.724 0.443 ILMN_2604226 Sema5a 20356 NM_009154.2 0.626 0.793 0.329 ILMN_2604224 Sema5a 20356 NM_009154.1 0.624 0.738 0.357 ILMN_2725927 Serpina3g 20715 NM_009251.1 0.837 0.664 0.450 ILMN_1246808 Serpine2 20720 AK045954 1.923 1.538 1.835 ILMN_2913166 Serping1 12258 NM_009776.1 0.931 0.676 0.589 ILMN_2775421 Serping1 12258 NM_009776 0.847 0.622 0.636 ILMN_2648169 Sfn 55948 NM_018754.1 3.318 2.327 3.659 ILMN_2645872 Sim2 20465 NM_011377.2 4.835 1.000 2.930 ILMN_2904117 Six1 20471 NM_009189.1 0.997 1.087 1.569 ILMN_1218617 Skiv2l2 72198 NM_028151.2 0.812 1.141 0.641 ILMN_2634317 Slc1a3 20512 NM_148938.2 0.613 0.389 0.312 ILMN_2838501 Slc24a3 94249 NM_053195.2 3.331 1.830 3.585 ILMN_2888144 Slc29a1 63959 NM_022880.1 1.993 1.415 2.532 ILMN_2747923 Slc40a1 53945 NM_016917.2 0.688 0.523 0.308 ILMN_1243388 Slc5a7 63993 NM_022025.3 2.069 1.220 1.864 ILMN_1257987 Slc7a3 11989 NM_007515.2 0.572 0.580 0.460 ILMN_2661340 Slco4a1 108115 NM_148933.1 5.718 1.000 7.619 ILMN_1253797 Slit2 20563 NM_178804.2 0.905 0.751 0.567 ILMN_1253925 Slit3 20564 AK019479 0.685 0.718 0.511 ILMN_2643545 Slit3 20564 XM_203363.3 0.708 0.931 0.553 ILMN_3153010 Slitrk5 75409 NM_198865.1 2.892 1.531 3.212 ILMN_2695150 Smc5 226026 NM_153808 0.611 0.785 0.781 ILMN_1225376 Smoc1 64075 NM_022316.1 6.255 2.061 5.962 ILMN_1247267 Smox 228608 NM_145533.1 1.278 1.503 1.599 ILMN_3136638 Snca 20617 NM_009221.2 0.689 0.779 0.532 ILMN_3161601 Snca 20617 NM_009221.2 0.528 0.639 0.365 ILMN_1220023 Snhg10 69434 NR_003145.2 1.324 1.529 1.563 ILMN_2490820 Snhg12 100039864 - 0.742 0.709 0.646 ILMN_2609614 Snx10 71982 NM_028035.3 0.534 0.645 0.491 ILMN_2628178 Socs2 216233 NM_007706.3 1.315 1.782 3.001 ILMN_2695085 Sorcs2 81840 NM_030889.2 0.651 0.861 0.550 Schäfer et al.

PROBE_ID SYMBOL GENE_ID ACCESSION Gadd45a -/- Ing1 -/- DKO

ILMN_2733114 Sp7 170574 NM_130458.1 3.156 0.753 4.245 ILMN_2795564 Speer3 71026 NM_027650.1 0.669 1.152 0.380 ILMN_2701129 Spef1 70997 XM_357260.1 0.691 0.629 0.588 ILMN_1243507 Spsb4 211949 NM_145134.2 1.948 1.608 2.339 ILMN_2629486 Srpx 51795 NM_016911.4 0.584 0.795 0.479 ILMN_1238000 Srpx 51795 NM_016911.4 0.600 0.748 0.543 ILMN_2695199 St3gal6 54613 NM_018784.2 2.709 1.086 1.529 ILMN_2777319 Stc1 20855 NM_009285.3 1.777 1.123 1.265 ILMN_2422982 Synpo 104027 - 0.825 0.779 0.664 ILMN_3127335 Sytl2 83671 NM_001040088.1 1.201 1.553 1.530 ILMN_3139514 Tbx3 21386 NM_011535.2 1.705 1.205 1.826 ILMN_1253515 Tbx4 21387 NM_011536 1.675 1.618 3.158 ILMN_1225196 Tgfb2 21808 NM_009367.2 1.297 1.206 1.797 ILMN_2834379 Tgfbi 21810 NM_009369.1 0.657 0.592 0.609 ILMN_2727663 Tgfbi 21810 NM_009369.3 0.588 0.559 0.389 ILMN_2760979 Tgfbr2 21813 NM_009371.2 0.738 0.804 0.605 ILMN_2789239 Tgfbr3 21814 NM_011578.2 0.729 0.628 0.429 ILMN_2692615 Tgm2 21817 NM_009373.3 0.819 0.550 0.955 ILMN_2760619 Tinagl1 94242 NM_023476.2 1.501 1.307 1.698 ILMN_2976129 Tinagl1 94242 NM_023476.1 1.415 1.163 1.507 ILMN_2599402 Tle1 21885 NM_011599.3 1.461 1.442 1.524 ILMN_1213001 Tmc6 217353 NM_145439.1 1.473 1.263 1.523 ILMN_3162005 Tmem204 407831 NM_001001183.1 0.507 0.962 0.371 ILMN_2589741 Tmem51 214359 NM_145402.3 0.664 0.755 0.279 ILMN_2881296 Tmem66 67887 NM_026432.2 0.731 1.441 1.949 ILMN_1258965 Tmem66 67887 NM_026432.2 0.945 0.829 0.550 ILMN_2479124 Tnfrsf26 244237 NM_175649.5 0.346 0.696 0.528 ILMN_2503052 Tnnc1 21924 NM_009393.2 1.130 1.037 1.620 ILMN_1225528 Trib3 228775 NM_175093.2 0.496 0.588 0.398 ILMN_2480463 Trim25 217069 NM_009546.2 0.840 0.842 0.659 ILMN_2510474 Tro 56191 NM_001002272.2 1.798 1.297 1.438 ILMN_1234698 Tspan2 70747 NM_027533.2 1.403 1.530 1.945 ILMN_2584195 Tulp4 68842 AK077171 1.098 1.280 1.504 ILMN_3112873 Txnip 56338 NM_001009935.2 0.533 0.861 0.647 ILMN_1213609 Txnip 56338 NM_023719.1 0.624 1.041 0.695 ILMN_1230019 Ube1l 74153 NM_023738.4 0.601 0.730 0.502 ILMN_2493826 Ugt1a10 394430 NM_201641.2 0.929 0.522 0.924 ILMN_2461668 Unc5c 22253 NM_009472.3 4.450 1.750 5.497 ILMN_2461665 Unc5c 22253 NM_009472 2.575 1.912 3.638 ILMN_2445165 Vdr 22337 NM_009504.2 0.489 0.552 0.547 ILMN_1218264 Vldlr 22359 NM_013703.1 0.693 0.592 0.591 ILMN_2515601 Vldlr 22359 NM_013703.1 0.792 0.745 0.618 ILMN_2421925 Wdfy1 69368 NM_027057 0.994 0.594 0.650 ILMN_2486906 Wisp2 22403 NM_016873.1 1.451 0.680 1.589 ILMN_1258734 Wnt2 22413 NM_023653.4 2.004 1.177 1.951 ILMN_2441346 Zcchc5 213436 NM_199468.1 2.738 0.855 1.273 ILMN_1247853 Zfp36l1 12192 NM_007564.4 0.750 0.789 0.658 ILMN_1256012 Zfp521 225207 NM_181326.3 0.804 0.674 0.601 ILMN_2721919 Zfp768 233890 NM_146202.1 1.570 1.950 2.073 ILMN_2739562 Zfp91-cntf 664779 NM_001039718.1 1.330 1.124 1.897 ILMN_1230858 - - AK034948 1.000 5.886 5.909 ILMN_2523281 - - - 1.246 1.072 1.577 ILMN_1230443 - - - 1.034 1.678 1.672

Note: The apparent Gadd45a gene induction in the Gadd45a mutants is due to the fact that the corresponding array probe targets the 3’ UTR gene region which is not deleted.

Significantly DOWN-regulated genes in each individual mutant sample:

# Gadd45a -/- : A730054J21Rik, Adamts2, Adh7, AI115600, Asns, Atp8b1, Cbx3, Ccl7, Cd40, Cd59a, Chac1, Chchd10, Cldn1, Csgalnact1, Ctse, Ctsk, Cxcl1, Cyb5r1, D0H4S114, Dcn, Dfna5h, Dpt, F2rl1, Fgf21, Htra1, Ifitm1, Il17rd, Itgbl1, Kif26b, Ldb2, LOC100046044, LOC100046802, LOC100047749, LOC633016, LOC638301, LOC669658, Lum, Med23, Mfap4, Mlkl, Mmp13, Mmp9, Moxd1, Nhsl2, Nt5c3, Osr2, Pcdhb22, Rassf8, Rbm20, Sema5a, Slc7a3, Smc5, Snx10, Srpx, Tmem204, Tnfrsf26, Trib3, Txnip, Vdr

Schäfer et al.

# Ing1 -/- : A230050P20Rik, Acot1, Adamts2, Adh7, AI316807, Capn6, Chchd10, Col24a1, Ctsc, Cxcl1, Cxcl14, Dcn, Fut10, Gadd45a, Gap43, Hsd3b7, Lmcd1, LOC100046044, Mlkl, Mmp13, Moxd1, Prelp, Ptx3, Ramp3, Rbm13, Slc1a3, Slc40a1, Slc7a3, Tgfbi, Tgm2, Trib3, Ugt1a10, Vdr, Vldlr, Wdfy1

# DKO : 1190002H23Rik, 1200009O22Rik, 2310047A01Rik, 2810022L02Rik, 5430435G22Rik, A230050P20Rik, A730054J21Rik, Abca3, Acat2, Acot1, Acss2, Adam23, Adamts2, Adamts4, Adamts9, Adh1, Adh7, Agap1, AI115600, AI316807, Angptl6, Ank2, Ankrd6, Apob48r, Arap1, Arhgdig, Asns, Atp8b1, BC006779, Bcl11b, Bicc1, C1qtnf2, C2, Cacna1g, Casp4, Cbx3, Ccl11, Ccl7, Cd40, Cd59a, Cdh3, Chac1, Chchd10, Chst15, Cldn1, Clec2d, Col15a1, Col24a1, Col6a1, Col6a2, Cox6a2, Crispld2, Csgalnact1, Ctsc, Ctsk, Cxadr, Cxcl1, Cxcl14, Cyp4a12a, D0H4S114, Dcn, Dhcr7, Dnmt3l, Dpt, Dtx3l, Ednra, EG630499, Enox1, Epha3, Etl4, Exosc5, F2rl1, Fads2, Fam129a, Fam13c, Fam169b, Fam20a, Fbln1, Fgf21, Flt1, Fut10, Fxyd6, Gap43, Gbp2, Gli2, Gpnmb, Gpt2, Gsdmdc1, H2-D1, H2-Q5, H2-T10, H2-T23, Hoxd8, Hs6st1, Hsd3b7, Htra1, Hvcn1, Ifitm1, Igfbp3, Igsf10, Iigp2, Il17rd, Irf9, Irx2, Itgbl1, Kcne4, Kif26b, Klhl24, Ldb2, Lgals3bp, Lgr5, LOC100038882, LOC100038993, LOC100040592, LOC100045439, LOC100046802, LOC100047260, LOC100047583, LOC633016, LOC637711, LOC638301, LOC641366, LOC669658, LOC674135, LOC674912, Lpin1, Lrrc15, Lrrc17, Lum, Mest, Mfap4, Mfhas1, Mgll, Mlkl, Mmp11, Mmp13, Mmp9, Moxd1, Mrgprf, Msx1, Mt1, Mtus1, Ndrg1, Neurl1a, Nfib, Nhsl2, Nod1, Nt5c3, Oasl2, Odz3, Odz4, Olfml3, Osr2, P2rx3, Parp14, Pcdhb22, Pcsk9, Pcyt1b, Pdgfra, Pdlim2, Plat, Ppp1r13b, Ppp1r3d, Prelp, Prickle1, Ptn, Rab3d, Ralgps2, Ramp3, Rassf8, Rbm13, Rbp1, Rerg, Rgma, Rnf213, Rora, Rtn4rl1, Samd9l, Scd2, Sema3f, Sema5a, Serpina3g, Serping1, Skiv2l2, Slc1a3, Slc40a1, Slc7a3, Slit2, Slit3, Snca, Snhg12, Snx10, Sorcs2, Speer3, Spef1, Srpx, Synpo, Tgfbi, Tgfbr2, Tgfbr3, Tmem204, Tmem51, Tmem66, Trib3, Trim25, Txnip, Ube1l, Vdr, Vldlr, Wdfy1, Zfp36l1, Zfp521

Significantly UP-regulated genes in each individual mutant sample:

# Gadd45a -/- : 2310001H12Rik, 2900026A02Rik, 9130213B05Rik, Abcb1b, Adap1, Aqp5, Atp1b1, Bdnf, Bmp4, Bves, C1qb, C1qc, C1qtnf3, Cbr2, Ccdc68, Cck, Cd52, Cgnl1, Chst1, Chst7, Cited2, Col2a1, Creb5, Crip2, D10Wsu102e, D14Ertd449e, Ddit4l, Dlk1, Dlx2, Dmpk, Dner, Dyrk3, Eno3, Enpp1, Erdr1, Fcer1g, Fcrls, Fgf10, Foxc1, Foxg1, Fst, Fxyd5, Gabrb3, Gjb3, Gnai1, Gper, Gprc5a, Grid2, Gsta4, Hist1h4h, Hmga2-ps1, Hoxa5, Hspb6, Id1, Il11, Il1rn, Kcnk6, Klf2, Klk8, Laptm5, Lhx9, Limch1, LOC100039175, LOC100044411, Lor, Lyz, Lyz2, Mboat1, Mcf2l, Mgp, Mgst3, Mid1, Mmp16, Mustn1, Myh11, Mylk, Ngfb, Nme7, Nptx2, Nrn1, Pcp4l1, Pde4dip, Pkp1, Plac9, Prrx2, Prss35, Rcan2, Rgs4, Sdc4, Serpine2, Sfn, Sim2, Slc24a3, Slc29a1, Slc5a7, Slco4a1, Slitrk5, Smoc1, Sp7, St3gal6, Stc1, Tbx3, Tro, Unc5c, Wnt2, Zcchc5

# Ing1 -/- : 9130213B05Rik, Aldh1a3, Ankrd1, Bmp4, C1qb, Chst2, Col2a1, D10Wsu102e, Dner, Emcn, Entpd4, Erdr1, Fcrls, Galntl4, Hmga2-ps1, Hoxa5, Hoxa7, Ide, LOC668047, Mgp, Mylk, Nek3, Ngfb, Pde4dip, Prss35, Rbpms, Serpine2, Smoc1, Socs2

# DKO : 1700112C13Rik, 2200002D01Rik, 2310001H12Rik, 2310039E09Rik, 2610014I16Rik, 2810003C17Rik, 2900026A02Rik, 6330407I18Rik, 6720475J19Rik, 9130213B05Rik, 9930013L23Rik, 9930105H17Rik, Accn3, Acpl2, Adamts12, Adamtsl3, Adap1, Adra2a, Ahrr, Ak1, Alcam, Aldh1a3, Ankrd1, Aoc3, Aqp5, Arg1, Atp1b1, Atp5sl, B230312A22Rik, B3gnt5, Baiap2l1, Bdnf, Bmp4, Bmpr1b, Bves, C030027H14Rik, C130021I20Rik, C1qtnf3, C230060E24, Cbr2, Ccdc68, Ccdc85b, Cck, Ccl17, Cdkn1a, Cflar, Cgnl1, Chst1, Chst7, Cited2, Cobll1, Col2a1, Copg, Creb5, Crim1, Crip2, Crlf1, Cstf3, Ctsh, D10Wsu102e, D14Ertd449e, Dap, Dbc1, Ddit4l, Des, Dlk1, Dlk2, Dmpk, Dner, Dusp4, Dusp5, Dyrk3, Dysf, EG633640, Elovl4, Emcn, Eno3, Enpp1, Entpd4, Epha2, Erdr1, Esm1, Fabp3, Fam65b, Fgf13, Fkhl18, Flrt1, Foxc1, Foxc2, Fst, Garnl3, Gata2, Gdf15, Gfod1, Gipc2, Gja1, Gjb2, Gjb3, Glis3, Gnai1, Gpr114, Gprc5a, Grem2, Grid2, Grin3a, Gsta4, Has2, Hbegf, Hey1, Hist1h4h, Hlx, Hmga2-ps1, Hoxa11as, Hoxa5, Hoxa7, Hspb1, Hspb6, Id1, Id2, Il11, Il1rn, Irf5, Jam2, Jph2, Kif5c, Klf2, Krt19, Lce1f, Lhx9, Limch1, LOC100039175, Lor, Masp1, Mcf2l, Meox1, Mgmt, Mgp, Mid1, Mmd, Mmp3, Mrvi1, Mtap6, Mtap9, Mustn1, Myh11, Mylk, Mylk2, Myocd, Myom1, Nbl1, Ndufaf4, Nek3, Nes, Ngfb, Nme7, Npal1, Npr3, Nptx2, Nqo1, Nrn1, Nuak2, Otud4, Pcp4l1, Pde1b, Pde4dip, Pdgfa, Pdk4, Pgf, Pgpep1, Phlda1, Pik3cb, Pkp1, Plac9, Plaur, Plod2, Polr2h, Ppap2a, Pparg, Ppp1r1a, Prrx2, Pvr, Rasal2, Rasgrp3, Rbfox1, Rbpms, Rcan2, Rem1, Rgs4, Ripk2, S100a13, Scx, Sdc4, Serpine2, Sfn, Six1, Slc24a3, Slc29a1, Slc5a7, Slco4a1, Slitrk5, Smoc1, Smox, Snhg10, Socs2, Spsb4, St3gal6, Sytl2, Tbx3, Tbx4, Tgfb2, Tinagl1, Tle1, Tmc6, Tmem66, Tnnc1, Tspan2, Tulp4, Unc5c, Wisp2, Zfp768, Zfp91-cntf

Schäfer et al.

Table S3 Gene class enrichment analysis of the list of 212 DKO-MEF down-regulated genes using DAVID 6.7 bioinformatics resources (Huang et al. 2009a; 2009b):

Number Fold Enrichment Bonferroni FDR Enriched Gene Ontology (GO) Term of Genes Enrichment P-Value correction (%)

GO:0005576~extracellular region 44 4.1 1.1E-16 1.7E-14 1.3E-13 GO:0044421~extracellular region part 32 5.4 4.8E-15 7.3E-13 5.8E-12 GO:0031012~extracellular matrix 20 6.3 1.4E-10 2.1E-08 1.7E-07 GO:0005578~proteinaceous extracellular matrix 19 6.4 4.0E-10 6.0E-08 4.8E-07 GO:0005886~plasma membrane 46 1.9 5.5E-06 8.2E-04 6.5E-03 GO:0005615~extracellular space 14 4.2 2.0E-05 3.0E-03 2.4E-02 GO:0035295~tube development 14 4.0 3.3E-05 3.9E-02 5.3E-02 GO:0001501~skeletal system development 14 4.0 4.1E-05 4.9E-02 6.7E-02 GO:0006955~immune response 13 4.3 4.3E-05 5.0E-02 6.9E-02 GO:0031226~intrinsic to plasma membrane 13 4.1 5.8E-05 8.6E-03 6.9E-02 GO:0022610~biological adhesion 15 3.3 1.5E-04 1.6E-01 2.4E-01 GO:0007155~cell adhesion 15 3.3 1.5E-04 1.6E-01 2.4E-01 GO:0005887~integral to plasma membrane 12 4.0 1.7E-04 2.4E-02 2.0E-01 GO:0030324~lung development 8 5.5 5.2E-04 4.7E-01 8.4E-01 GO:0004175~endopeptidase activity 11 3.8 5.4E-04 1.5E-01 7.2E-01 GO:0030323~respiratory tube development 8 5.4 5.8E-04 5.0E-01 9.3E-01 GO:0009611~response to wounding 10 3.9 8.7E-04 6.5E-01 1.4E+00 GO:0060541~respiratory system development 8 5.0 9.6E-04 6.8E-01 1.5E+00 GO:0008203~cholesterol metabolic process 6 7.6 9.6E-04 6.8E-01 1.5E+00

Note: The background list for this analysis consisted of all genes with clear expression in the control (wild-type) MEF sample (detection P-value of 0). Similar enrichment results were obtained also using the default DAVID background list containing all annotated mouse genes. Schäfer et al.

Supplemental Materials and Methods

In vitro pull-down assay

His-tag pull down assay was carried out essentially as described (Yi et al. 2000) using in vitro translated proteins (Reticulocyte Lysate, TNT, Promega) following manufacturer’s instructions. 10% of the protein amount used for pull down is shown as Input.

Reporter constructs

The pGL3 promoter luciferase reporter (pGL3-Luc), containing the SV40 promoter was from

Promega. The rDNA promoter luciferase reporter and the Oct4TK-GFP reporter were described previously (Barreto et al. 2007; Schmitz et al. 2009).

Genotyping

Adults and embryos were genotyped by gene-specific triplex PCRs using the following primers.

Gene Primer Sequence Amplicon size Ing1 WT f 5`- GCC ACA ATT GCC ACA ATT TC 233 bp KO f 5`- CCT TCT ATC GCC TTC TTG ACG 200 bp r 5`- GTC TGT GTG GCA TCA TGG TC Gadd45a f 5`- CCT CTG CTT ACC TCT GCA CAA WT r 5`- GAA GAC CTA GAC AGC ACG GTT 324 bp KO r 5`- AGA ACG AGA TCA GCA GCC TCT 211 bp

Primer sequences and predesigned UPL monocolor hydrolysis probe (Roche) for expression analysis by qPCR Designation RT Primer Sequence UPL No hING1a f 5`-ATG TTG AGT CCT GCC AAC G #39 r 5`- GAG TCC AGG TAG TCC TCC ACA hING1b f 5`-TGG ACG AGT TGA TTT GAA CG #19 r 5`-AGC AGC GAG AAG AAC CAA TC hGADD45a f 5`-GCC AAG CTG CTC AAC GTC #40 r 5`-CTC TGT CGT CGT CCT CGT C hGADD45b f 5`-AGT CGG CCA AGT TGA TGA AT #13 r 5`-CCT CCT CCT CCT CGT CAA T Schäfer et al.

Designation RT Primer Sequence UPL No hMAGEB2 f 5`-GCC ATA GCC AAT CAA TCT CC #62 r 5`-AAG ACC TCA TTG GGG GTG A hDHRS2 f 5`- TGA GAC TAT CAC CTA TCG CCA AG #4 r 5`- CAG CAT AGT GGT TGG TGT CTG hFTCD f 5`- CGA GGC ATT TAA GGA CCA GA #75 r 5`- AGT GCA GCC TGG GTC TTG hARC f 5`- TCC TCA AAT CCG GCT GAG #21 r 5`- TTT GTG GGA ACC TTG AGA CC hTCEAL7 f 5`- CAG ACA TCT GGG GGA AGA AA #15 r 5`- TGC AGG GTT TTT GCA TGA T hVGF f 5`- TCC CGA TCT TCC CCT GTC #39 r 5`- CGG AAG CCG ACA ATC TGA hTAF7L f 5`- AAT TTA GAA ATG GGG TCT TGT TAT GT #64 r 5`- TGG TGG TGC ACA ACT GTA GTC hWDR5 f 5`-GCG TAT GAT GGG AAA TTT GAG #33 r 5`-TGA CGA CCA GGC TAC ATC G hGAPDH f 5`-GCA TCC TGG GCT ACA CTG AG #82 r 5`-AGG TGG AGG AGT GGG TGT C mIng1a f 5` -CCT CCT TCT CGT CCA GAT TG #17 r 5` -TCT CCC GTT TGA ACT TCT CAT AG mIng1b f 5` -ATC GAC GCC AAA TAC CAA GA #17 r 5` -CGT CTG TCT CCC GTT TGA A mIng1c f 5` -GAT CGC TTG TCG CGT TTC #17 r 5` -TGT CTC CCG TTT GAA CTT CTC mGadd45a f 5` -GCT GCC AAG CTG CTC AAC #98 r 5` -TCG TCG TCT TCG TCA GCA mGadd45b f 5` -CTG CCT CCT GGT CAC GAA #10 r 5` -TTG CCT CTG CTC TCT TCA CA mGadd45g f 5` -GGA TAA CTT GCT GTT CGT GGA #76 r 5`-AAG TTC GTG CAG TGC TTT CC mMageb1-3 f 5`- GCA CAG TCC CTA GTG CCT TC #51 r 5`- CAC CCT TGC CTT GAA CTC TC mMageb4 f 5`- TCA GGA AGA GAG AGC CCA AG #13 r 5`- CAG CCT GAT ATT TGC AAG AGG mCxcl1 f 5`- AGA CTC CAG CCA CAC TCC AA #83 r 5`- TGA CAG CGC AGC TCA TTG mHoxd8 f 5`- AAT GTT TCC CTG GAT GAG ACC #17 r 5`- CTA GGG TTT GGA AGC GAC TG mWdr5 f 5`- GCC TAG TCC AGC AGA TCG TC #70 r 5`- GCT GTC AGC TGA ACT CTA TAG TAA GG mG6pd f 5`- GAA AGC AGA GTG AGC CCT TC #78 r 5`- CAT AGG AAT TAC GGG CAA AGA GFP f 5`- CCT GAA GTT CAT CTG CAC CA #37 r 5`- GGT CAG GGT GGT CAC GAG

Schäfer et al.

Primer sequences and predesigned UPL monocolor hydrolysis probe (Roche) for ChIP or MS-PCR analyses

Designation ChIP Primer Sequence UPL No hMAGEB2 “a” f 5`- TTG GGT CAG CAC GCA TAT T #64 r 5`- CGT CTC CAC TAG GGT CCT CA hMAGEB2 “b” f 5`- TGA GAG GCT CCG GTA AAG C #37 r 5`- GCG TCC AAA CCT CCT TCC hMAGEB2 “c” f 5`- AAG TGA ACG ACC CCA TTA AAG A #64 r 5`- TCC CAA AGT GCT GGG ATT AC hMAGEB2 “d” f 5`- ACC CGG GGT CTC AAT GTT #6 r 5`- CCA GAA ACA GAA GAG GAA CAG C hMAGEB2 for f 5`- CGT CCC AGG CTG CTA GAT AC SYBR MS-PCR r 5`- ATC CGC TCG GGT CTT TTT green hDHRS2 f 5`- TCC TGT CCC GAC AAA AGG #18 r 5`- AGA GGA ATC CAG TCT CCT TGG hTCEAL7 f 5`- AGA GAT CAT TTG AAA ATA GTT CAC CTC #77 r 5`- CCC ACT CCT CAC CCT CAG hTAF7L f 5`- TTG CAT TCT TCC CTA CAG AGG SYBR r 5`- TGT TAT GAA ACA TGA TTT CGT CTT C green hGAPDH f 5`- CGT AGC TCA GGC CTC AAG AC #23 r 5`- GCT GCG GGC TCA ATT TAT AG hCo f 5`- CTC TAT TGT CCC TCC TGC TTA GTA TT #42 (intergenic) r 5`- TGG GAC TCC CTG CTA AGA CA mMageb2”a” f 5`- TTT TCG AGG GGG CTA ATA GG #52 r 5`- AGA CCC ACT AAA GCG ACC ATA C mMageb2”a’ ” f 5`- CTA GGG TTA TCT AAA ACG CAG ACA T #34 r 5`- TGG TAG CAC ATG CAT TTA ACC T mMageb2”b” f 5`- TGG ATA TTT TTC CCA GCT TCC #49 r 5`- TCA TAA GGA AGG TGT CTG TTG GTA mMageb2”c” f 5`- TGG GTC TAT ATG TAT AGG GCT TGC #17 r 5`- CCT ATA CAG ACA AGA TTA GGC CAC T mMageb2”d” f 5`- GGA AGC CTA ACT GGG TTG TAT G #43 r 5`- AAA CCC ATT AAT GCC ACC AT mMageb2”e” f 5`- CGG AAG TCC TGG TAT GTT CC #2 r 5`- TGG AGA CCT GGC TTT TGA AG mMageb2”f” f 5`- GGG AGG TTC CAG TAG TTC AGC #6 r 5`- GAC CCA GCA CTC TGG TCA AC mMageb2”g” f 5`- CAC AGT CCC TAG TGC CTT CC #51 r 5`- ACC CTT GCC TTG AAC TCT CC mMageb2”h” f 5`- TGG CAG CTG CAA TTT TAT CA #49 r 5`- CCA TTC CTG CAG GCT CAT mMageb4 f 5`- CAG TTG GAA AGT CTC AGA GAG TAG AG #48 r 5`- TGT GGT GGT ATG GGT GCT C mCxcl1 f 5`- CAG GGT GTT TCC CTG CAA #52 r 5`- TCC TTG GGA GTG GAG CAA mHoxd8 f 5`- GCA GGA CTT TGA TTC GCT TT #75 r 5`- GGG CCT AGC TAA GTG GTT TTG mGapdh f 5`- CCT ACG CAG GTC TTG CTG A #14 r 5`- TGA CCT TGA GGT CTC CTT GG

Schäfer et al.

Primer sequences for bisulfite sequencing

Designation Bisulfite sequencing Primer Sequence hMAGEB2 f 5`- ATA TTG AGG TGA GGA TTT TAG TGG A r 5`- TAA ATT CAC CCC TAC TAC CA hDHRS2 f 5`- GTT GTT TAG GAA TTG TGA AGA AAT TG r 5`- CCA ATC AAA AAC TAA AAC CCC TTA T hTAF7L f 5`- TAG AAT ATT TAT GTA AGT GGT TTT TAG G r 5`- ATA TAC AAT TAA ACA ATA CCT TAT TTA ACA mCxcl1 f 5`- CTA ACC AAA AAT CTT CTC CCA TAA A r 5`- TTA AGG GAG TTT TAG GGT TAA GGT AAG mHoxd8 f 5`- GTT TGG TTG GAA AAA GTA GGA TTT r 5`- CAA CCT TAA AAA AAA CCC ATA AAA C pGL3-Luc f 5`- TTG TAT TTT AAT TAG TTA GTA ATT ATA GTT r 5`- TTC CAT AAT AAC TTT ACC AAC AAT ACC Oct4TK-GFP f 5`- GAT TTG TTT TGT AGG TGG AGA GTT T r 5`- AAA TAA ACT TCA AAA TCA ACT TAC C

Primer sequences for ING1bW235A point-mutagenesis

Designation Primer Sequence W235A f 5`- GAG TGC CCC ATC GAG GCG TTC CAC TTC TCG TG r 5`- CAC GAG AAG TGG AAC GCC TCG ATG GGG CAC TC

Supplemental References

Barreto G, Schäfer A, Marhold J, Stach D, Swaminathan SK, Handa V, Doderlein G, Maltry N, Wu W, Lyko F et al. 2007. Gadd45a promotes epigenetic gene activation by repair- mediated DNA demethylation. Nature 445: 671-675. Huang DW, Sherman BT, Lempicki RA. 2009a. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37: 1-13. Huang DW, Sherman BT, Lempicki RA. 2009b. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature protocols 4: 44-57. Schmitz KM, Schmitt N, Hoffmann-Rohrer U, Schafer A, Grummt I, Mayer C. 2009. TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation. Mol Cell 33: 344-353. Yi YW, Kim D, Jung N, Hong SS, Lee HS, Bae I. 2000. Gadd45 family proteins are coactivators of nuclear hormone receptors. Biochem Biophys Res Commun 272: 193- 198.