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E-GEOD-31320 - Genome-wide identification of functional elements regulated by T-bet and GATA3 in human T-cells

Status
Released on 16 November 2012, last updated on 10 December 2012
Organism
Homo sapiens
Samples (5)
Protocols (3)
Description
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. 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.
Experiment type
ChIP-seq 
Contacts
Aditi Kanhere <a.kanhere@ucl.ac.uk>, Arnulf Hertweck, Graham M Lord, Richard Jenner
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
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