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Series GSE19198 Query DataSets for GSE19198
Status Public on Jan 08, 2010
Title Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 TFs
Organism Mus musculus
Experiment type Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design 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.
Contributor(s) Kwon H, Thierry-Mieg D, Thierry-Mieg J, Oh J, Leonard WJ
Citation(s) 20064451
Submission date Nov 25, 2009
Last update date May 15, 2019
Contact name Warren J Leonard
Phone 301-496-0098
Organization name NHLBI/NIH
Lab MSC 1674
Street address 10 Center Dr
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (2)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
GPL9250 Illumina Genome Analyzer II (Mus musculus)
Samples (56)
GSM475957 S10SG_Ctrl_1
GSM475958 S10SG_Ctrl_2
GSM475959 S10SG_Ctrl_3
SRA SRP001688
BioProject PRJNA120861

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Supplementary file Size Download File type/resource
GSE19198_RAW.tar 70.8 Mb (http)(custom) TAR (of CEL)
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Raw data are available in SRA
Processed data included within Sample table

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