STANDARD_NAME GSE19198_1H_VS_24H_IL21_TREATED_TCELL_DN SYSTEMATIC_NAME M7230 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE19198_1H_VS_24H_IL21_TREATED_TCELL_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes down-regulated in T cells treated with IL21 [GeneID=59067]: 1h versus 24h. DESCRIPTION_FULL Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4. PMID 20064451 GEOID GSE19198 AUTHORS Kwon H,Thierry-Mieg D,Thierry-Mieg J,Kim HP,Oh J,Tunyaplin C,Carotta S,Donovan CE,Goldman ML,Tailor P,Ozato K,Levy DE,Nutt SL,Calame K,Leonard WJ CONTRIBUTOR Jernej Godec CONTRIBUTOR_ORG Dana-Farber Cancer Institute EXACT_SOURCE GSE19198_2368_200_DN FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ABCC3,ABI2,ADAM12,ADO,AFTPH,ALDH5A1,ALG8,AMICA1,AMPD2,ANO10,ANXA11,APOL3,ARAP3,ARL6IP5,ARNTL2,ATP1B1,ATP6V0D2,BCAR3,BID,BIRC3,BRPF1,BTG3,C10orf54,C11orf21,C17orf96,C1orf115,C1orf54,C2orf89,C9orf46,CABIN1,CARD9,CBX6,CCDC115,CCL17,CCL5,CCNA1,CCR7,CD1B,CD274,CD40,CD44,CD48,CD83,CD86,CDK14,CDS1,CHST7,CR1,CSF2RB,CYLD,CYP1B1,CYTH4,CYTL1,DDX27,DHRS7,DIAPH1,DNAJC4,DNAJC5B,EGR2,EHD1,EHF,EMB,FAM129B,FAM69A,FARSB,FAS,FCHO1,FCHSD2,FOLR3,G6PC3,GALNTL4,GSTK1,HBEGF,HK3,HLA-B,HLA-G,HLA-J,HMGN2P46,HMGN3,HSD11B1,HTATIP2,HYAL3,IFIH1,IL2RG,ISOC1,ITGAL,ITGAM,ITPRIPL1,KIAA0564,KLHL5,KYNU,LGALS2,LILRA1,LITAF,LOC100132891,LOC100505746,LOC100507057,LOC285628,LOC644090,LPCAT4,LRRC33,LRRC39,LRRFIP2,LY75,LY9,MANF,MB21D2,ME1,METTL1,MICAL2,MICALL2,MID1IP1,MOBKL2B,MSC,MYCL1,MYOF,NAA25,NCF2,NFAM1,NME7,NR4A3,OAS2,OCIAD1,OVOL1,PAPSS1,PDCD4,PEA15,PELP1,PEMT,PHPT1,PLBD1,PLCB1,PLCD1,PLEK,PMAIP1,POLR1B,PPARGC1B,PPP1R14A,PSME2,PSTPIP1,PTGS1,PTPRE,RAP1GAP,RASAL2,RASGRP1,RIPK2,RNF122,ROBO3,SARDH,SEMA7A,SFXN4,SIL1,SLAMF7,SLC24A4,SLC25A12,SLC25A29,SLC25A45,SLC27A3,SLC29A3,SLC2A6,SLC7A11,SNAP23,SOX4,SPINK1,SRD5A3,SRGN,SRSF7,STARD7,SVIL,SYTL1,TAPT1,TBC1D23,TBC1D9,TIMP3,TMEM91,TNFAIP6,TNFSF10,TNFSF13B,TOR3A,TP53I13,TRAF1,TRAF3,TRERF1,TSPAN32,TSPAN33,TTYH2,TUBA1A,TUBB6,TXNDC3,UBA7,VARS,VILL,WDR74,XAF1,XPO6,YIF1B,ZBTB46,ZFYVE16,ZGLP1,ZNF711 GENE_SYMBOLS ABCC3,ABI2,ADAM12,ADO,AFTPH,ALDH5A1,ALG8,JAML,AMPD2,ANO10,ANXA11,APOL3,ARAP3,ARL6IP5,BMAL2,ATP1B1,ATP6V0D2,BCAR3,BID,BIRC3,BRPF1,BTG3,VSIR,C11orf21,EPOP,C1orf115,C1orf54,TRABD2A,PLGRKT,CABIN1,CARD9,CBX6,CCDC115,CCL17,CCL5,CCNA1,CCR7,CD1B,CD274,CD40,CD44,CD48,CD83,CD86,CDK14,CDS1,CHST7,CR1,CSF2RB,CYLD,CYP1B1,CYTH4,CYTL1,DDX27,DHRS7,DIAPH1,DNAJC4,DNAJC5B,EGR2,EHD1,EHF,EMB,NIBAN2,DIPK1A,FARSB,FAS,FCHO1,FCHSD2,FOLR3,G6PC3,GALNT18,GSTK1,HBEGF,HK3,HLA-B,HLA-G,HLA-J,HMGN2P46,HMGN3,HSD11B1,HTATIP2,HYAL3,IFIH1,IL2RG,ISOC1,ITGAL,ITGAM,ITPRIPL1,VWA8,KLHL5,KYNU,LGALS2,LILRA1,LITAF,MSC-AS1,ITGB2-AS1,MELTF-AS1,MIR3142HG,PRKAG2-AS2,LPCAT4,NRROS,LRRC39,LRRFIP2,LY75,LY9,MANF,MB21D2,ME1,METTL1,MICAL2,MICALL2,MID1IP1,MOB3B,MSC,MYCL,MYOF,NAA25,NCF2,NFAM1,NME7,NR4A3,OAS2,OCIAD1,OVOL1,PAPSS1,PDCD4,PEA15,PELP1,PEMT,PHPT1,PLBD1,PLCB1,PLCD1,PLEK,PMAIP1,POLR1B,PPARGC1B,PPP1R14A,PSME2,PSTPIP1,PTGS1,PTPRE,RAP1GAP,RASAL2,RASGRP1,RIPK2,RNF122,ROBO3,SARDH,SEMA7A,SFXN4,SIL1,SLAMF7,SLC24A4,SLC25A12,SLC25A29,SLC25A45,SLC27A3,SLC29A3,SLC2A6,SLC7A11,SNAP23,SOX4,SPINK1,SRD5A3,SRGN,SRSF7,STARD7,SVIL,SYTL1,TAPT1,TBC1D23,TBC1D9,TIMP3,TMEM91,TNFAIP6,TNFSF10,TNFSF13B,TOR3A,TP53I13,TRAF1,TRAF3,TRERF1,TSPAN32,TSPAN33,TTYH2,TUBA1A,TUBB6,NME8,UBA7,VARS1,VILL,WDR74,XAF1,XPO6,YIF1B,ZBTB46,ZFYVE16,ZGLP1,ZNF711 FOUNDER_NAMES