ArrayExpress Uploader05909not specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiednot specifiedarrayexpress_sid6Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which...20064451E-GEOD-19198/profile/8773/arrayexpressuploader320cellcytokinegasgenomeinterleukinplasma cellspleenDec.12, 2014Falseanalysis-of-interleukin-21-induced-prdm1-gene-reguE-GEOD-19198_A-AFFY-45Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 TFsNov.11, 2014Interleukin-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. Affymetrix expression data: Prepare CD4+ T cells from spleen. CD4+ T cells were preactivated, rested, and treated with IL-21 for 1, 6, and 24 hours. ChIP-seq data: Profiling of IRF4 and Stat3 binding with and without IL-21 stimulation in wild type and IRF4 KO mice.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-19198mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-19198/samples/