The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes
- 20 October 2009
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (42), 17876-17881
- https://doi.org/10.1073/pnas.0909357106
Abstract
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 genomic map of T-bet and GATA-3 binding in primary human T cells and identify their target genes, most of which are previously unknown. In Th1 cells, T-bet associates with genes of diverse function, including those with roles in transcriptional regulation, chemotaxis and adhesion. GATA-3 occupies genes in both Th1 and Th2 cells and, unexpectedly, shares a large proportion of targets with T-bet. Re-complementation of T-bet alters the expression of these genes in a manner that mirrors their differential expression between Th1 and Th2 lineages. These data show that the choice between Th1 and Th2 lineage commitment is the result of the opposing action of T-bet and GATA-3 at a shared set of target genes and may provide a general paradigm for the interaction of lineage-specifying transcription factors.Keywords
This publication has 44 references indexed in Scilit:
- The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammationNature Immunology, 2009
- TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt functionNature, 2008
- Communicable Ulcerative Colitis Induced by T-bet Deficiency in the Innate Immune SystemCell, 2007
- Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfβ binding to the Il4 silencerThe Journal of Experimental Medicine, 2007
- Phenotypic and functional features of human Th17 cellsThe Journal of Experimental Medicine, 2007
- Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing transcription of the gene encoding interferon-γNature Immunology, 2007
- GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cellsBlood, 2007
- Control of Developmental Regulators by Polycomb in Human Embryonic Stem CellsCell, 2006
- EZH2 and Histone 3 Trimethyl Lysine 27 Associated with Il4 and Il13 Gene Silencing in TH1 CellsOnline Journal of Public Health Informatics, 2005
- Identification of a Conserved GATA3 Response Element Upstream Proximal from the Interleukin-13 Gene LocusOnline Journal of Public Health Informatics, 2002