STANDARD_NAME DUTERTRE_ESTRADIOL_RESPONSE_24HR_DN SYSTEMATIC_NAME M2157 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/DUTERTRE_ESTRADIOL_RESPONSE_24HR_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes down-regulated in MCF7 cells (breast cancer) at 24 h of estradiol [PubChem=5757] treatment. DESCRIPTION_FULL Alternative promoters (AP) occur in >30% protein-coding genes and contribute to proteome diversity. However, large-scale analyses of AP regulation are lacking, and little is known about their potential physiopathologic significance. To better understand the transcriptomic effect of estrogens, which play a major role in breast cancer, we analyzed gene and AP regulation by estradiol in MCF7 cells using pan-genomic exon arrays. We thereby identified novel estrogen-regulated genes (ERG) and determined the regulation of AP-encoded transcripts in 150 regulated genes. In <30% cases, APs were regulated in a similar manner by estradiol, whereas in >70% cases, they were regulated differentially. The patterns of AP regulation correlated with the patterns of estrogen receptor alpha (ERalpha) and CCCTC-binding factor (CTCF) binding sites at regulated gene loci. Interestingly, among genes with differentially regulated (DR) APs, we identified cases where estradiol regulated APs in an opposite manner, sometimes without affecting global gene expression levels. This promoter switch was mediated by the DDX5/DDX17 family of ERalpha coregulators. Finally, genes with DR promoters were preferentially involved in specific processes (e.g., cell structure and motility, and cell cycle). We show, in particular, that isoforms encoded by the NET1 gene APs, which are inversely regulated by estradiol, play distinct roles in cell adhesion and cell cycle regulation and that their expression is differentially associated with prognosis in ER(+) breast cancer. Altogether, this study identifies the patterns of AP regulation in ERGs and shows the contribution of AP-encoded isoforms to the estradiol-regulated transcriptome as well as their physiopathologic significance in breast cancer. PMID 20406972 GEOID AUTHORS Dutertre M,Gratadou L,Dardenne E,Germann S,Samaan S,Lidereau R,Driouch K,de la Grange P,Auboeuf D CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 3S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AASS,ABCA1,ABCC3,ABCC5,ABCG1,ABCG2,ABHD4,ABLIM3,ACAA2,ACHE,ACOX3,ACSL3,ACVR1,ADAM9,ADFP,AHR,ALCAM,ALDH1A3,ALS2CR16,ANK3,ANKRD50,ANXA2,ANXA3,AQP3,ARHGAP12,ARHGAP5,ARID4B,ARL4C,ATP10D,ATP1B1,ATP2B1,ATP6V0A4,ATP8A1,AXUD1,AYTL1,B4GALT4,BAK1,BASP1,BAZ2B,BCAP29,BCAS1,BCKDHB,BEXL1,BMF,BMP7,BOK,BTG2,C10orf118,C1orf103,C1orf106,C6orf166,C8orf72,CAB39,CALCOCO1,CALD1,CAMK2N1,CAPN13,CAST,CBLB,CCNDBP1,CCNG2,CD24,CD46,CD47,CD55,CDC42BPA,CDH2,CDH3,CDK6,CDKL5,CDKN1A,CDKN2A,CDKN2B,CDS1,CDYL2,CEACAM6,CENTD1,CGN,CITED2,CLDN1,CLDN4,CLDN9,CLK1,CLN8,CMKOR1,CMYA5,CNN2,COBLL1,COQ10B,CORO2A,CPEB2,CPEB4,CRABP2,CREB3L2,CRIM1,CRISPLD2,CSRP1,CTGF,CTNND2,CTSH,CXorf23,CYB5R1,CYP1A1,DAB2,DAPK3,DBN1,DCAMKL1,DDIT3,DDIT4,DIAPH2,DIO2,DKK1,DMRTA1,DNAJB2,DNAJC15,DOCK11,DSCR1,DTX3L,DUSP1,DUSP10,DUSP4,EDG3,EDN1,EFHD1,EFNA1,EFNB2,EGLN3,EGR1,ELF3,ELMOD2,EMB,ENC1,ENSG00000006459,ENSG00000042062,ENSG00000064042,ENSG00000100100,ENSG00000101608,ENSG00000109618,ENSG00000114127,ENSG00000122694,ENSG00000129292,ENSG00000131378,ENSG00000135241,ENSG00000135245,ENSG00000136044,ENSG00000136048,ENSG00000137628,ENSG00000145133,ENSG00000145911,ENSG00000150347,ENSG00000152926,ENSG00000158406,ENSG00000159784,ENSG00000162069,ENSG00000162458,ENSG00000164023,ENSG00000164463,ENSG00000164548,ENSG00000164654,ENSG00000164823,ENSG00000167767,ENSG00000168143,ENSG00000168675,ENSG00000170452,ENSG00000176018,ENSG00000178401,ENSG00000183742,ENSG00000184305,ENSG00000185305,ENSG00000185567,ENSG00000186088,ENSG00000188576,ENSG00000189066,ENSG00000198919,ENTPD3,EPAS1,EPB41,EPB41L2,EPB41L5,EPHA4,EPHA7,EPOR,ERBB2,ERRFI1,ETFA,EVA1,EVI1,EVI5,EXT1,FAM49B,FAM59A,FAM79A,FAM84A,FAT4,FBN1,FBN2,FBXO32,FBXO38,FCHO2,FHL2,FN1,FNBP1L,FRAS1,FRMD6,FTH1,FZD2,FZD7,GAB1,GABBR2,GADD45A,GALNT10,GARNL4,GATA6,GDF15,GOLGA4,GPR115,GPR126,GPR37,GPR81,GPR98,GRAMD1A,GRAMD3,GRB14,GRB7,GRHL3,GSTM2,GSTM3,GUCY1A2,GULP1,HBP1,HERC3,HES1,HIVEP2,HOXC13,HPS3,IBRDC2,ID3,IER5,IFIT1,IFIT5,IFNGR1,IGFBP3,IL13RA1,IL1R1,IRF6,ITGAV,ITGB6,ITGB8,ITSN2,JARID1B,JMJD1A,JMJD3,JUN,JUNB,KAL1,KCNJ3,KIAA0513,KIAA0802,KIAA0953,KIAA1109,KIAA1217,KIAA1946,KIF3A,KIFC3,KLF3,KLF5,KLF6,KLHL24,KLHL5,KYNU,L1CAM,LAMB1,LARP6,LFNG,LGALS8,LHFPL2,LIMA1,LIPH,LMBRD1,LMCD1,LMO7,LNX1,LOXL2,LRRC1,LYST,MAOA,MAP2,MAP3K14,MAP3K5,MAP3K8,MAP4K4,MARCKS,MATN2,MCCC1,MCL1,ME1,MGAT4A,MID1,MME,MMP16,MOSPD1,MSRB3,MSX2,MTAP,MYADM,MYH9,MYO1B,MYO1E,MYO6,NBEA,NBEAL1,NBPF8,NCF2,NCOA7,NEDD4L,NEDD9,NFKBIZ,NPAS2,NPHP3,NTN4,NUAK1,NUAK2,OACT2,OFD1,OPTN,ORMDL3,OSIL,PACS1,PALLD,PAM,PARP12,PARP14,PARP8,PARP9,PAWR,PBEF1,PCAF,PCDH1,PCDH9,PCTP,PDE5A,PDE9A,PDLIM1,PDLIM5,PGM2L1,PGM5,PHACTR2,PHF20L1,PHLDA3,PHLDB1,PHLDB2,PIK3C2B,PIK3R3,PINK1,PLA2R1,PLEKHC1,PLEKHF2,PLK2,PNRC1,PPARG,PPL,PPM2C,PPP1R15B,PPP1R3C,PPP2R5B,PPP3CC,PPP4R2,PRICKLE1,PRR5,PRSS8,PSD3,PTGER4,PTPN12,PTPRK,PVRL4,QKI,RAB27B,RAB9A,RAPGEF2,RASD1,RASEF,RBMS1,RGAG4,RGL1,RHOC,RIPK4,RIT1,RND1,RND3,RNF19,ROCK2,RPS6KC1,RWDD2,S100A10,SALL4,SAMD4A,SART2,SASH1,SCHIP1,SCN1B,SEC15L2,SEMA7A,SENP2,SERPINB1,SERTAD4,SESN2,SESN3,SFMBT2,SH2D4A,SH3BGRL2,SH3BP4,SH3YL1,SIM2,SKIL,SLC17A5,SLC31A2,SLC35A1,SLC39A10,SLC4A7,SLC9A1,SLCO2A1,SLIT2,SMAD3,SMYD2,SNAI2,SNTB2,SOCS2,SOS2,SOX4,SRI,ST3GAL1,ST8SIA4,STAM2,STK38L,STON1,SYDE2,SYNPO,SYTL2,TACC1,TACSTD2,TAGLN,TAOK3,TAX1BP1,TBC1D23,TCF7L1,TCP11L2,TFAP2A,TFPI,TGFB2,TGFB3,TGFBI,TGFBR2,TJP2,TLE1,TLOC1,TM4SF1,TMEM16F,TMEM30A,TMEM45B,TMEM46,TMEM65,TMEPAI,TMPRSS2,TNFRSF21,TNS3,TOM1L2,TP53INP1,TP73L,TPM4,TRAF5,TRAM2,TRIB1,TRIM16,TRIM5,TSC22D3,TSPAN12,TUFT1,UACA,UBE1DC1,UBE2H,UBE2J1,UBLCP1,UBP1,UGP2,UGT1A6,UNC13D,UPK1A,USP2,UTX,VPS54,VTCN1,WWC2,WWTR1,YPEL2,YPEL5,ZBTB37,ZDHHC17,ZDHHC7,ZFP36L1,ZKSCAN1,ZNF12,ZNF217,ZNF277,ZNF281,ZNF354A,ZNF561,ZNF654,ZNF704,ZSCAN2,ZYX GENE_SYMBOLS AASS,ABCA1,ABCC3,ABCC5,ABCG1,ABCG2,ABHD4,ABLIM3,ACAA2,ACHE,ACOX3,ACSL3,ACVR1,ADAM9,PLIN2,AHR,ALCAM,ALDH1A3,NBEAL1,ANK3,ANKRD50,ANXA2,ANXA3,AQP3,ARHGAP12,ARHGAP5,ARID4B,ARL4C,ATP10D,ATP1B1,ATP2B1,ATP6V0A4,ATP8A1,CSRNP1,LPCAT2,B4GALT4,BAK1,BASP1,BAZ2B,BCAP29,BCAS1,BCKDHB,BEX4,BMF,BMP7,BOK,BTG2,CCDC186,LRIF1,INAVA,AKIRIN2,FAM110B,CAB39,CALCOCO1,CALD1,CAMK2N1,CAPN13,CAST,CBLB,CCNDBP1,CCNG2,CD24,CD46,CD47,CD55,CDC42BPA,CDH2,CDH3,CDK6,CDKL5,CDKN1A,CDKN2A,CDKN2B,CDS1,CDYL2,CEACAM6,ARAP2,CGN,CITED2,CLDN1,CLDN4,CLDN9,CLK1,CLN8,ACKR3,CMYA5,CNN2,COBLL1,COQ10B,CORO2A,CPEB2,CPEB4,CRABP2,CREB3L2,CRIM1,CRISPLD2,CSRP1,CCN2,CTNND2,CTSH,BCLAF3,CYB5R1,CYP1A1,DAB2,DAPK3,DBN1,DCLK1,DDIT3,DDIT4,DIAPH2,DIO2,DKK1,DMRTA1,DNAJB2,DNAJC15,DOCK11,RCAN1,DTX3L,DUSP1,DUSP10,DUSP4,S1PR3,EDN1,EFHD1,EFNA1,EFNB2,EGLN3,EGR1,ELF3,ELMOD2,EMB,ENC1,KDM7A,RIPOR3,LIMCH1,PIK3IP1,MYL12A,SEPSECS,XRN1,GLIPR2,PHF20L1,RFTN1,PNPLA8,HILPDA,APPL2,DRAM1,DDX60,,N4BP3,ARID5B,ZNF117,H4C8,FAM131B,BICDL2,FBLIM1,SGMS2,CREBRF,TRA2A,MIOS,OSGIN2,KRT80,FAM83B,LDLRAD4,,LYSMD3,DNAJC22,MACC1,CCSER1,ARL15,AHNAK2,GSAP,,,DZIP3,ENTPD3,EPAS1,EPB41,EPB41L2,EPB41L5,EPHA4,EPHA7,EPOR,ERBB2,ERRFI1,ETFA,MPZL2,MECOM,EVI5,EXT1,CYRIB,GAREM1,TPRG1L,LRATD1,FAT4,FBN1,FBN2,FBXO32,FBXO38,FCHO2,FHL2,FN1,FNBP1L,FRAS1,FRMD6,FTH1,FZD2,FZD7,GAB1,GABBR2,GADD45A,GALNT10,RAP1GAP2,GATA6,GDF15,GOLGA4,ADGRF4,ADGRG6,GPR37,HCAR1,ADGRV1,GRAMD1A,GRAMD2B,GRB14,GRB7,GRHL3,GSTM2,GSTM3,GUCY1A2,GULP1,HBP1,HERC3,HES1,HIVEP2,HOXC13,HPS3,RNF144B,ID3,IER5,IFIT1,IFIT5,IFNGR1,IGFBP3,IL13RA1,IL1R1,IRF6,ITGAV,ITGB6,ITGB8,ITSN2,KDM5B,KDM3A,KDM6B,JUN,JUNB,ANOS1,KCNJ3,KIAA0513,MTCL1,EFR3B,BLTP1,KIAA1217,FAM171B,KIF3A,KIFC3,KLF3,KLF5,KLF6,KLHL24,KLHL5,KYNU,L1CAM,LAMB1,LARP6,LFNG,LGALS8,LHFPL2,LIMA1,LIPH,LMBRD1,LMCD1,LMO7,LNX1,LOXL2,LRRC1,LYST,MAOA,MAP2,MAP3K14,MAP3K5,MAP3K8,MAP4K4,MARCKS,MATN2,MCCC1,MCL1,ME1,MGAT4A,MID1,MME,MMP16,MOSPD1,MSRB3,MSX2,MTAP,MYADM,MYH9,MYO1B,MYO1E,MYO6,NBEA,NBEAL1,NBPF8,NCF2,NCOA7,NEDD4L,NEDD9,NFKBIZ,NPAS2,NPHP3,NTN4,NUAK1,NUAK2,MBOAT2,OFD1,OPTN,ORMDL3,SQSTM1,PACS1,PALLD,PAM,PARP12,PARP14,PARP8,PARP9,PAWR,NAMPT,KAT2B,PCDH1,PCDH9,PCTP,PDE5A,PDE9A,PDLIM1,PDLIM5,PGM2L1,PGM5,PHACTR2,PHF20L1,PHLDA3,PHLDB1,PHLDB2,PIK3C2B,PIK3R3,PINK1,PLA2R1,FERMT2,PLEKHF2,PLK2,PNRC1,PPARG,PPL,PDP1,PPP1R15B,PPP1R3C,PPP2R5B,PPP3CC,PPP4R2,PRICKLE1,PRR5,PRSS8,PSD3,PTGER4,PTPN12,PTPRK,NECTIN4,QKI,RAB27B,RAB9A,RAPGEF2,RASD1,RASEF,RBMS1,RTL5,RGL1,RHOC,RIPK4,RIT1,RND1,RND3,RNF19A,ROCK2,RPS6KC1,RWDD2A,S100A10,SALL4,SAMD4A,DSE,SASH1,SCHIP1,SCN1B,EXOC6B,SEMA7A,SENP2,SERPINB1,SERTAD4,SESN2,SESN3,SFMBT2,SH2D4A,SH3BGRL2,SH3BP4,SH3YL1,SIM2,SKIL,SLC17A5,SLC31A2,SLC35A1,SLC39A10,SLC4A7,SLC9A1,SLCO2A1,SLIT2,SMAD3,SMYD2,SNAI2,SNTB2,SOCS2,SOS2,SOX4,SRI,ST3GAL1,ST8SIA4,STAM2,STK38L,STON1,SYDE2,SYNPO,SYTL2,TACC1,TACSTD2,TAGLN,TAOK3,TAX1BP1,TBC1D23,TCF7L1,TCP11L2,TFAP2A,TFPI,TGFB2,TGFB3,TGFBI,TGFBR2,TJP2,TLE1,SEC62,TM4SF1,ANO6,TMEM30A,TMEM45B,SHISA2,TMEM65,PMEPA1,TMPRSS2,TNFRSF21,TNS3,TOM1L2,TP53INP1,TP63,TPM4,TRAF5,TRAM2,TRIB1,TRIM16,TRIM5,TSC22D3,TSPAN12,TUFT1,UACA,UBA5,UBE2H,UBE2J1,UBLCP1,UBP1,UGP2,UGT1A6,UNC13D,UPK1A,USP2,KDM6A,VPS54,VTCN1,WWC2,WWTR1,YPEL2,YPEL5,ZBTB37,ZDHHC17,ZDHHC7,ZFP36L1,ZKSCAN1,ZNF12,ZNF217,ZNF277,ZNF281,ZNF354A,ZNF561,ZNF654,ZNF704,ZSCAN2,ZYX FOUNDER_NAMES