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Status |
Public on Nov 16, 2012 |
Title |
Genome-wide identification of functional elements regulated by T-bet and GATA3 in human T-cells |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
T-bet and GATA3 induce differentiation of CD4+ T-cells into Th1 or Th2 effectors. These exhibit a range of different properties but understanding of T-bet and GATA3 function is mostly limited to the murine Ifng and Il4/Il5/Il13 loci. We hypothesised that extending such analyses across the human genome would allow further insight into T-bet and GATA3 function. We have discovered that T-bet and GATA3 bind to multiple distal sites at a set of key immune regulatory genes. These sites display markers of functional elements, act as enhancers in reporter assays and are associated with lineage-specific expression regulated by T-bet and GATA3. Our approach also reveals that GATA3 is distributed at T-bet binding sites in Th1 cells and that T-bet directly activates its own expression. We propose that these aspects of T-bet and GATA3 function are critical for Th1/ Th2 differentiation and provide a model for the relationship between other lineage-specific regulators.
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Overall design |
ChIP was performed using antibody against T-bet in Th1 cells and against GATA3 in Th1 cells as well as Th2 cells. A sample of whole cell extract (WCE) from Th1 cells and Th2 cells was sequenced. Th1 WCE was used as the background to determine enrichment.
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Contributor(s) |
Kanhere A, Hertweck A, Lord GM, Jenner R |
Citation(s) |
23232398 |
Submission date |
Aug 10, 2011 |
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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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) |
GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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Samples (5)
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Relations |
SRA |
SRP007861 |
BioProject |
PRJNA146093 |