The Transcription Factors T-bet and GATA-3 Control Alternative Pathways of T-cell Differentiation Through a Shared Set of Target Genes
Author(s)Young, Richard A.; Jenner, Richard G.; Townsend, Michael J.; Jackson, Ian; Sun, Kaiming; Bouwman, Russell D.; Glimcher, Laurie H.; Lord, Graham M.; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences (U.S.)
Jenner, Richard G., Michael J. Townsend, Ian Jackson, Kaiming Sun, Russell D. Bouwman, Richard A. Young, Laurie H. Glimcher, and Graham M. Lord. "The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes." Proceedings of the National Academy of Sciences 106 (October 2009): 17876-17881.
Final published version
Genomic map, T helper differentiation, Cytokines