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Title: Genome-wide regulatory analysis reveals T-bet controls Th17 lineage differentiation through direct suppression of IRF4      
keywords:
Epigenomics
ID:
PRJNA174603
description:
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.
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA174603
authentication:
none
authorization:
none
ID:
pmid:24249732
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • 091009/Wellcome Trust/United Kingdom

  • G1000758/Medical Research Council/United Kingdom

  • MR/J006742/1/Medical Research Council/United Kingdom

  • PG/12/36/29444/British Heart Foundation/United Kingdom

  • MR/K002996/1/Medical Research Council/United Kingdom

  • Wellcome Trust/United Kingdom

  • G0801537/Medical Research Council/United Kingdom

  • G0802068/Medical Research Council/United Kingdom

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