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Supplementary Table S2: Defining AR-Regulated DNA Repair Genes

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Supplementary table S2: Defining AR-regulated DNA repair genes GE t-test p-value AR Binding Location AR bound DEG venn Gene GE log2 (1881/DMSO) Total AIFM1 0.24 0.076146983 NA 0 0 Neither 32 ALKBH1 0.28 0.024552195 Enh 1 1 both 42 ALKBH2 0.40 0.024502762 NA 0 1 GE 31 ALKBH3 0.21 0.16044799 Enh 1 0 Chip 39 APC 0.08 0.638163337 Enh 1 0 Chip 144 APTX 0.33 0.024049352 NA 0 1 GE ASF1A 0.18 0.288385847 NA 0 0 Neither ATR 0.45 0.017251675 Enh 1 1 both ATRX 0.02 0.928064314 Enh 1 0 Chip ATXN3 -0.10 0.397119237 Enh 1 0 Chip BRCC3 0.29 0.027339474 NA 0 1 GE BRE -0.03 0.822180421 Enh 1 0 Chip CCNH 0.67 0.000983785 Enh 1 1 both CDK7 0.09 0.395014007 Enh 1 0 Chip CEBPG 0.44 0.001560472 NA 0 1 GE CETN3 0.36 0.016164106 NA 0 1 GE CHEK1 0.79 0.000453806 Enh 1 1 both CIB1 0.23 0.121407592 NA 0 0 Neither CRY1 0.16 0.203816244 Enh 1 0 Chip DCLRE1A 0.32 0.061293389 Enh 1 0 Chip DCLRE1C 0.21 0.091378952 Enh 1 0 Chip DDB1 0.11 0.304164484 NA 0 0 Neither EEF1E1 0.43 0.003736071 NA 0 1 GE ERCC1 0.11 0.356043612 NA 0 0 Neither ERCC2 0.24 0.050052886 NA 0 0 Neither ERCC3 0.09 0.390828823 NA 0 0 Neither ERCC5 0.12 0.185931114 NA 0 0 Neither ERCC6 0.19 0.120922784 Enh 1 0 Chip ERCC8 0.28 0.060618097 Enh 1 0 Chip FANCC 0.70 0.000276058 Enh 1 1 both FANCI 1.22 0.000116513 Enh 1 1 both FANCL 0.20 0.113308242 NA 0 0 Neither FANCM 0.60 0.001211228 NA 0 1 GE GADD45G -0.19 0.195513334 NA 0 0 Neither GTF2H1 0.28 0.02419552 NA 0 1 GE GTF2H2 -0.15 0.543518124 NA 0 0 Neither GTF2H3 0.40 0.018710774 NA 0 1 GE GTF2H5 0.25 0.083106721 NA 0 0 Neither HMGB2 1.18 0.000245067 NA 0 1 GE HUS1 0.38 0.017973598 Enh 1 1 both LIG3 0.33 0.009930616 Enh 1 1 both LIG4 -0.04 0.644397617 NA 0 0 Neither MAD2L1 1.24 3.04E-05 Enh 1 1 both MAP2K6 0.21 0.138474822 Enh 1 0 Chip MBD4 0.32 0.042290985 NA 0 1 GE MBD5 -0.22 0.045745568 Enh 1 0 Chip MCM7 0.88 0.000962329 Prom 1 1 both MLH1 0.40 0.005549413 NA 0 1 GE MLH3 0.12 0.254752752 NA 0 0 Neither MNAT1 -0.06 0.697399765 Enh 1 0 Chip MRE11A 0.56 0.008055228 Enh 1 1 both MSH2 0.36 0.0255032 Enh 1 1 both MSH3 0.13 0.142781513 Enh 1 0 Chip MSH5 0.68 0.013242841 NA 0 1 GE MSH6 0.54 0.001535356 Enh 1 1 both MYO6 0.17 0.13153906 Prom 1 0 Chip N4BP2 0.16 0.271676796 Enh 1 0 Chip NAE1 0.36 0.007997236 NA 0 1 GE NBN 0.33 0.01619791 Enh 1 1 both NEK11 0.05 0.868742423 Enh 1 0 Chip PALB2 0.34 0.001994449 NA 0 1 GE PARP1 0.46 0.007749876 Enh 1 1 both PCNA 0.96 0.000130721 NA 0 1 GE PMS1 0.28 0.088726937 Enh 1 0 Chip PMS2 -0.37 0.006463055 Enh 1 0 Chip PMS2L4 -0.38 0.195532085 NA 0 0 Neither POLA1 0.73 0.000222029 Enh 1 1 both POLA2 1.02 0.000129191 Enh 1 1 both POLB 0.12 0.470428782 NA 0 0 Neither POLD2 0.61 0.001675355 NA 0 1 GE POLD3 0.74 0.000184499 NA 0 1 GE POLE 0.53 0.001734271 NA 0 1 GE POLE2 1.48 0.001568106 Enh 1 1 both POLG2 0.14 0.256729073 NA 0 0 Neither POLK -0.09 0.359706553 NA 0 0 Neither POLN 0.33 0.404858162 Enh 1 0 Chip POLR2A 0.24 0.107558219 NA 0 0 Neither POLR2B 0.16 0.125931655 Enh 1 0 Chip POLR2C 0.18 0.154398833 NA 0 0 Neither POLR2D 0.46 0.014007488 NA 0 1 GE POLR2F 0.47 0.029587477 NA 0 1 GE POLR2H 0.37 0.019711326 NA 0 1 GE POLR2I 0.36 0.048865033 NA 0 1 GE POLR2J 0.26 0.086558477 NA 0 0 Neither POLR2K 0.30 0.045426436 NA 0 1 GE RAD17 0.24 0.067513455 NA 0 0 Neither RAD18 0.86 0.000547006 Enh 1 1 both RAD21 0.50 0.001471156 Enh 1 1 both RAD50 0.29 0.051067453 NA 0 0 Neither RAD51AP1 1.27 8.30E-05 NA 0 1 GE RAD51C 0.81 0.000934463 Enh 1 1 both RAD51L1 0.57 0.043952229 NA 0 1 GE RAD54B 0.99 0.00027001 Enh 1 1 both RBBP4 0.17 0.219344812 Enh 1 0 Chip RECQL 0.47 0.000355482 NA 0 1 GE RECQL5 0.17 0.250285408 NA 0 0 Neither REV1 0.20 0.136102881 Enh 1 0 Chip RFC1 0.39 0.007029186 Enh 1 1 both RFC3 1.04 0.000329283 Enh 1 1 both RFC4 0.87 0.000242486 Enh 1 1 both RFC5 0.87 0.001063776 NA 0 1 GE RIF1 0.59 0.026592108 NA 0 1 GE RINT1 0.28 0.074657138 NA 0 0 Neither RPA1 0.38 0.010832747 NA 0 1 GE RPA2 0.66 0.001666583 NA 0 1 GE RPAIN 0.16 0.1994445 NA 0 0 Neither RRM1 0.85 0.000689702 NA 0 1 GE RRM2B 0.08 0.527875163 Enh 1 0 Chip RUVBL2 0.61 0.002869175 NA 0 1 GE SESN1 -0.21 0.108139452 Enh 1 0 Chip SHFM1 0.29 0.027106879 Enh 1 1 both SMC1A 0.58 0.001272919 NA 0 1 GE SOD1 0.21 0.120810011 NA 0 0 Neither SSBP1 0.36 0.026384905 NA 0 1 GE SUMO1 0.17 0.18999283 NA 0 0 Neither TDG 0.33 0.036466782 NA 0 1 GE TDP1 0.25 0.047588975 Enh 1 1 both TERF1 -0.01 0.92749992 Enh 1 0 Chip TINF2 0.09 0.430242052 NA 0 0 Neither TOP2B 0.15 0.235621984 Enh 1 0 Chip TOPBP1 0.70 0.000588496 Enh 1 1 both TOPORS 0.12 0.240082418 NA 0 0 Neither UBB 0.17 0.18196271 NA 0 0 Neither UBE2A 0.10 0.287278904 NA 0 0 Neither UBE2B 0.10 0.35693834 NA 0 0 Neither UBE2D2 0.24 0.095096399 NA 0 0 Neither UBE2D3 0.18 0.163241149 NA 0 0 Neither UBE2L3 0.27 0.073153226 Enh 1 0 Chip UBE2N 0.24 0.07093839 Enh 1 0 Chip UBE2V1 0.22 0.072186123 NA 0 0 Neither UBE2V2 0.24 0.057660451 NA 0 0 Neither UNG 0.63 0.003530096 NA 0 1 GE UPF1 0.40 0.01538213 NA 0 1 GE USP1 0.44 0.007797246 Enh 1 1 both UVRAG 0.12 0.412508278 Enh 1 0 Chip VCP 0.19 0.114817639 NA 0 0 Neither WDR33 0.28 0.01897993 NA 0 1 GE WRN 0.22 0.016912034 Enh 1 1 both XAB2 0.30 0.03900428 NA 0 1 GE XPC 0.04 0.670064278 NA 0 0 Neither XRCC4 0.48 0.031276365 Enh 1 1 both XRCC5 0.34 0.015147221 Enh 1 1 both XRCC6 0.37 0.016636685 NA 0 1 GE XRCC6BP1 0.33 0.027218813 NA 0 1 GE (3) those that are direct AR (1) the list of (2) those of the 144 genes targets genes annotated for peak 144 induced by androgens or enhancer Class both AIFM1 ALKBH1 ALKBH1 ge ALKBH1 ALKBH2 ATR chip ALKBH2 APTX CCNH neither ALKBH3 ATR CHEK1 Sum APC BRCC3 FANCC APTX CCNH FANCI ASF1A CEBPG HUS1 ATR CETN3 LIG3 ATRX CHEK1 MAD2L1 ATXN3 EEF1E1 MCM7 BRCC3 FANCC MRE11A BRE FANCI MSH2 CCNH FANCM MSH6 CDK7 GTF2H1 NBN CEBPG GTF2H3 PARP1 CETN3 HMGB2 POLA1 CHEK1 HUS1 POLA2 CIB1 LIG3 POLE2 CRY1 MAD2L1 RAD18 DCLRE1A MBD4 RAD21 DCLRE1C MCM7 RAD51C DDB1 MLH1 RAD54B EEF1E1 MRE11A RFC1 ERCC1 MSH2 RFC3 ERCC2 MSH5 RFC4 ERCC3 MSH6 SHFM1 ERCC5 NAE1 TDP1 ERCC6 NBN TOPBP1 ERCC8 PALB2 USP1 FANCC PARP1 WRN FANCI PCNA XRCC4 FANCL POLA1 XRCC5 FANCM POLA2 GADD45G POLD2 GTF2H1 POLD3 GTF2H2 POLE GTF2H3 POLE2 GTF2H5 POLR2D HMGB2 POLR2F HUS1 POLR2H LIG3 POLR2I LIG4 POLR2K MAD2L1 RAD18 MAP2K6 RAD21 MBD4 RAD51AP1 MBD5 RAD51C MCM7 RAD51L1 MLH1 RAD54B MLH3 RECQL MNAT1 RFC1 MRE11A RFC3 MSH2 RFC4 MSH3 RFC5 MSH5 RIF1 MSH6 RPA1 MYO6 RPA2 N4BP2 RRM1 NAE1 RUVBL2 NBN SHFM1 NEK11 SMC1A PALB2 SSBP1 PARP1 TDG PCNA TDP1 PMS1 TOPBP1 PMS2 UNG PMS2L4 UPF1 POLA1 USP1 POLA2 WDR33 POLB WRN POLD2 XAB2 POLD3 XRCC4 POLE XRCC5 POLE2 XRCC6 POLG2 XRCC6BP1 POLK POLN POLR2A POLR2B POLR2C POLR2D POLR2F POLR2H POLR2I POLR2J POLR2K RAD17 RAD18 RAD21 RAD50 RAD51AP1 RAD51C RAD51L1 RAD54B RBBP4 RECQL RECQL5 REV1 RFC1 RFC3 RFC4 RFC5 RIF1 RINT1 RPA1 RPA2 RPAIN RRM1 RRM2B RUVBL2 SESN1 SHFM1 SMC1A SOD1 SSBP1 SUMO1 TDG TDP1 TERF1 TINF2 TOP2B TOPBP1 TOPORS UBB UBE2A UBE2B UBE2D2 UBE2D3 UBE2L3 UBE2N UBE2V1 UBE2V2 UNG UPF1 USP1 UVRAG VCP WDR33 WRN XAB2 XPC XRCC4 XRCC5 XRCC6 XRCC6BP1.
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    FANCJ regulates the stability of FANCD2/FANCI proteins and protects them from proteasome and caspase-3 dependent degradation Komaraiah Palle, Ph.D. (Kumar) Assistant Professor of Oncologic Sciences Abraham Mitchell Cancer Research Scholar Mitchell Cancer Institute University of South Alabama Outline • Fanconi anemia (FA) pathway • Role of FA pathway in Genome maintenance • FANCJ and FANCD2 functional relationship • FANCJ-mediated DDR in response to Fork-stalling Fanconi Anemia • Rare, inherited blood disorder. • 1:130,000 births Guido Fanconi 1892-1979 • Affects men and women equally. • Affects all racial and ethnic groups – higher incidence in Ashkenazi Jews and Afrikaners Birth Defects Fanconi anemia pathway • FA is a rare chromosome instability syndrome • Autosomal recessive disorder (or X-linked) • Developmental abnormalities • 17 complementation groups identified to date • FA pathway is involved in DNA repair • Increased cancer susceptibility - many patients develop AML - in adults solid tumors Fanconi Anemia is an aplastic anemia FA patients are prone to multiple types of solid tumors • Increased incidence and earlier onset cancers: oral cavity, GI and genital and reproductive tract head and neck breast esophagus skin liver brain Why? FA is a DNA repair disorder • FA caused by mutations in 17 genes: FANCA FANCF FANCM FANCB FANCG/XRCC9 FANCN/PALB2 FANCC FANCI RAD51C/FANCO FANCD1/BRCA2 FANCJ SLX4/FANCP FANCD2 FANCL ERCC2/XPF/FANCQ FANCE BRCA1/FANCS • FA genes function in DNA repair processes • FA patient cells are highly sensitive
  • The Middle Temporal Gyrus Is Transcriptionally Altered in Patients with Alzheimer’S Disease

    The Middle Temporal Gyrus Is Transcriptionally Altered in Patients with Alzheimer’S Disease

    1 The middle temporal gyrus is transcriptionally altered in patients with Alzheimer’s Disease. 2 1 3 Shahan Mamoor 1Thomas Jefferson School of Law 4 East Islip, NY 11730 [email protected] 5 6 We sought to understand, at the systems level and in an unbiased fashion, how gene 7 expression was most different in the brains of patients with Alzheimer’s Disease (AD) by mining published microarray datasets (1, 2). Comparing global gene expression profiles between 8 patient and control revealed that a set of 84 genes were expressed at significantly different levels in the middle temporal gyrus (MTG) of patients with Alzheimer’s Disease (1, 2). We used 9 computational analyses to classify these genes into known pathways and existing gene sets, 10 and to describe the major differences in the epigenetic marks at the genomic loci of these genes. While a portion of these genes is computationally cognizable as part of a set of genes 11 up-regulated in the brains of patients with AD (3), many other genes in the gene set identified here have not previously been studied in association with AD. Transcriptional repression, both 12 pre- and post-transcription appears to be affected; nearly 40% of these genes are transcriptional 13 targets of MicroRNA-19A/B (miR-19A/B), the zinc finger protein 10 (ZNF10), or of the AP-1 repressor jun dimerization protein 2 (JDP2). 14 15 16 17 18 19 20 21 22 23 24 25 26 Keywords: Alzheimer’s Disease, systems biology of Alzheimer’s Disease, differential gene 27 expression, middle temporal gyrus.