Article abstract
Nature Immunology 8, 145 - 153 (2006)
Published online: 31 December 2006 | doi:10.1038/ni1424
Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells
Ivana M Djuretic1, Ditsa Levanon2, Varda Negreanu2, Yoram Groner2, Anjana Rao1 & K Mark Ansel1
Abstract
Cell differentiation involves activation and silencing of lineage-specific genes. Here we show that the transcription factor Runx3 is induced in T helper type 1 (TH1) cells in a T-bet-dependent manner, and that both transcription factors T-bet and Runx3 are required for maximal production of interferon-
(IFN-) and silencing of the gene encoding interleukin 4 (Il4) in TH1 cells. T-bet does not repress Il4 in Runx3-deficient TH2 cells, but coexpression of Runx3 and T-bet induces potent repression in those cells. Both T-bet and Runx3 bind to the Ifng promoter and the Il4 silencer, and deletion of the silencer decreases the sensitivity of Il4 to repression by either factor. Our data indicate that cytokine gene expression in TH1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing.
- Harvard Medical School and the CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA.
- Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Correspondence to: K Mark Ansel1 e-mail: ansel@cbr.med.harvard.edu
Correspondence to: Anjana Rao1 e-mail: arao@cbr.med.harvard.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Regulation of T H I differentiation ? controlling the controllersNature Immunology News and Views (01 Jun 2002)
Shaping a helper T cell identityNature Immunology News and Views (01 Feb 2007)
See all 9 matches for News And ViewsRESEARCH
Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20Nature Structural Biology Article (01 Mar 2000)
See all 52 matches for Research
