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| 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
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| 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.
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| Overall design |
ChIP-seq analysis of T-bet in WT and Tbet -/- mice.
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| Contributor(s) |
Gökmen MR, Kanhere A, Jenner R, Lord G |
| Citation(s) |
24249732 |
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| Submission date |
Sep 05, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Aditi Kanhere |
| E-mail(s) |
a.kanhere@liverpool.ac.uk
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| Organization name |
University of Liverpool
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| Lab |
Kanhere Lab
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| Street address |
Institute of Systems, Molecular and Integrative Biology
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| City |
Liverpool |
| ZIP/Postal code |
L69 3GE |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA174603 |
| SRA |
SRP015481 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE40623_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of BED, BW, TXT) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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