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Series GSE39756 Query DataSets for GSE39756
Status Public on Sep 18, 2012
Title BATF-JUN is critical for IRF4-mediated transcription in T cells
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Interferon regulatory factor 4 (IRF4) is an IRF family transcription factor with critical roles in lymphoid development and in regulating the immune response. IRF4 binds DNA weakly owing to a carboxy-terminal auto-inhibitory domain, but cooperative binding with factors such as PU.1 or SPIB in B cells increases binding affinity, allowing IRF4 to regulate genes containing ETS–IRF composite elements (EICEs; 5'-GGAAnnGAAA-3'). Here we show that in mouse CD4+ T cells, where PU.1/SPIB expression is low, and in B cells, where PU.1 is well expressed, IRF4 unexpectedly can cooperate with activator protein-1 (AP1) complexes to bind to AP1–IRF4 composite (5'-TGAnTCA/GAAA-3') motifs that we denote as AP1–IRF composite elements (AICEs). Moreover, BATF–JUN family protein complexes cooperate with IRF4 in binding to AICEs in pre-activated CD4+ T cells stimulated with IL-21 and in TH17 differentiated cells. Importantly, BATF binding was diminished in Irf4-/- T cells and IRF4 binding was diminished in Batf-/- T cells, consistent with functional cooperation between these factors. Moreover, we show that AP1 and IRF complexes cooperatively promote transcription of the Il10 gene, which is expressed in TH17 cells and potently regulated by IL-21. These findings reveal that IRF4 can signal via complexes containing ETS or AP1 motifs depending on the cellular context, thus indicating new approaches for modulating IRF4-dependent transcription.
Overall design Genome-wide transcription factors mapping and binding of IRF4, BATF, IRF8, STAT3, JUN etc in WT, Irf4-/- and Batf-/- mice in different cell types (B cells, CD4+ T cells and TH17 cells) cultured with or without IL-21 was conducted. RNA-Seq is conducted in mouse B cells, CD4+ T cells, TH1/TH2/TH9/TH17/Treg.
Contributor(s) Li P, Spolski R, Liao W, Wang L, Murphy TL, Murphy KM, Leonard WJ
Citation(s) 22992523
Submission date Jul 30, 2012
Last update date May 15, 2019
Contact name Peng Li
Organization name NIH
Department NHLBI
Street address 9000 Rockville Pike
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (3)
GPL9185 Illumina Genome Analyzer (Mus musculus)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (38)
GSM978746 WT Bcell IgG
GSM978747 WT Bcell -IL21 IRF4
GSM978748 WT Bcell +IL21 IRF4
BioProject PRJNA171705
SRA SRP014628

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Supplementary file Size Download File type/resource
GSE39756_RAW.tar 4.9 Gb (http)(custom) TAR (of BED, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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