期刊
NATURE COMMUNICATIONS
卷 3, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms2260
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资金
- Wellcome Trust grant [091009]
- MRC Career Development award
- MRC grant [G0802068]
- MRC Centre for Medical Molecular Virology [G0900950]
- Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre award
- MRC [G0802068, G0900950] Funding Source: UKRI
- Medical Research Council [MR/J006742/1, G0802068, G0900950] Funding Source: researchfish
- National Institute for Health Research [CL-2010-17-010] Funding Source: researchfish
T-bet and GATA3 regulate the CD4+ T cell Th1/Th2 cell fate decision but little is known about the interplay between these factors outside of the murine Ifng and Il4/Il5/Il13 loci. Here we show that T-bet and GATA3 bind to multiple distal sites at immune regulatory genes in human effector T cells. These sites display markers of functional elements, act as enhancers in reporter assays and are associated with a requirement for T-bet and GATA3. Furthermore, we demonstrate that both factors bind distal sites at Tbx21 and that T-bet directly activates its own expression. We also show that in Th1 cells, GATA3 is distributed away from Th2 genes, instead occupying T-bet binding sites at Th1 genes, and that T-bet is sufficient to induce GATA3 binding at these sites. We propose these aspects of T-bet and GATA3 function are important for Th1/Th2 differentiation and for understanding transcription factor interactions in other T cell lineage decisions.
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