GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE40623 Query DataSets for GSE40623
Status Public on Dec 03, 2013
Title Genome-wide regulatory analysis reveals T-bet controls Th17 lineage differentiation through direct suppression of IRF4
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The complex relationship between Th1 and Th17 cells is incompletely understood. The transcription factor T-bet is best known as the master regulator of Th1 lineage commitment. However, attention is now focused on the repression of alternate T cell subsets mediated by T-bet, particularly the Th17 lineage. Specifically it has recently been suggested that pathogenic Th17 cells express T-bet and are dependent on IL-23. However, T-bet has previously been shown to be a negative regulator of Th17 cells. We have taken an unbiased approach to determine the functional impact of T-bet on Th17 lineage commitment. Genome-wide analysis of functional T-bet binding sites provides an improved understanding of the transcriptional regulation mediated by T-bet, and suggests novel mechanisms by which T-bet regulates T helper cell differentiation. Specifically, we show that T-bet negatively regulates Th17 lineage commitment via direct repression of the transcription factor interferon regulatory factor-4 (IRF4). An in vivo analysis of the pathogenicity of T-bet deficient T cells demonstrated that Th17 responses were augmented in the absence of T-bet, and we have defined a critical temporal window for T-bet function. The interaction of the two key transcription factors T-bet and IRF4 during the determination of T cell fate choice significantly advances our understanding of the mechanisms underlying the development of pathogenic T cells.
Overall design ChIP-seq analysis of T-bet in WT and Tbet -/- mice.
Contributor(s) Gökmen MR, Kanhere A, Jenner R, Lord G
Citation(s) 24249732
Submission date Sep 05, 2012
Last update date May 15, 2019
Contact name Aditi Kanhere
Organization name University of Liverpool
Street address Institute of Systems, Molecular and Integrative Biology
City Liverpool
ZIP/Postal code L69 3GE
Country United Kingdom
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (3)
GSM998271 Th1_WCE
GSM998272 Th1_Tbet
GSM998273 Th1_Tbet -/-
BioProject PRJNA174603
SRA SRP015481

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE40623_RAW.tar 1.2 Gb (http)(custom) TAR (of BED, BW, TXT)
SRA Run SelectorHelp
Processed data provided as supplementary file
Raw data are available in SRA

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap