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Omics score: 5

Comparative genomic hybridization and transcription profiling of human and mouse T cells in differentiation

ABSTRACT: ChIP-Chip for T-bet and GATA-3 in human Th1 and Th2 cells, gene expression profiling of human Th1 and Th2 cells and of T-cells from T-bet-deficient mice,

ORGANISM(S): Musculus

SUBMITTER: Richard Jenner

PROVIDER: E-TABM-759 | ArrayExpress | 2009-10-26

REPOSITORIES: ArrayExpress

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The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes.

Jenner Richard G RG Townsend Michael J MJ Jackson Ian I Sun Kaiming K Bouwman Russell D RD Young Richard A RA Glimcher Laurie H LH Lord Graham M GM

Proceedings of the National Academy of Sciences of the United States of America 20091005 42

Upon detection of antigen, CD4(+) T helper (Th) cells can differentiate into a number of effector types that tailor the immune response to different pathogens. Alternative Th1 and Th2 cell fates are specified by the transcription factors T-bet and GATA-3, respectively. Only a handful of target genes are known for these two factors and because of this, the mechanism through which T-bet and GATA-3 induce differentiation toward alternative cell fates is not fully understood. Here, we provide a geno ...[more]

PMID: 19805038

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

Project 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.

2012-11-16 | E-GEOD-31320 | ArrayExpress

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