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Chromatin remodeling by the SWI/SNF-like BAF complex and STAT4 activation synergistically induce IL-12Rbeta2 expression during human Th1 cell differentiation.

Abstract : Interleukin-12 (IL-12) is a key cytokine for the development of T helper type 1 (Th1) responses; however, naive CD4(+) T cells do not express IL-12Rbeta2, and are therefore unresponsive to IL-12. We have examined the mechanisms that control Th1-specific expression of the human IL-12Rbeta2 gene at early time points after T-cell stimulation. We have identified a Th1-specific enhancer element that binds signal transducer and activator of transcription 4 (STAT4) in vivo in developing Th1 but not Th2 cells. T-cell receptor (TCR) signaling induced histone hyperacetylation and recruitment of BRG1, the ATPase subunit of the SWI/SNF-like BAF chromatin remodeling complex, to the IL-12Rbeta2 regulatory regions and was associated with low-level gene transcription at the IL-12Rbeta2 locus. However, high-level IL-12Rbeta2 expression required TCR triggering in the presence of IL-12. Our results indicate a synergistic role of TCR-induced chromatin remodeling and cytokine-induced STAT4 activation to direct IL-12Rbeta2 expression during Th1 cell development.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00161615
Contributor : Marie-Dominique Aytac <>
Submitted on : Wednesday, July 11, 2007 - 11:02:48 AM
Last modification on : Thursday, May 28, 2020 - 5:24:03 PM

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Fabrice A. Letimier, Nadia Passini, Sonia Gasparian, Elisabetta Bianchi, Lars Rogge. Chromatin remodeling by the SWI/SNF-like BAF complex and STAT4 activation synergistically induce IL-12Rbeta2 expression during human Th1 cell differentiation.. EMBO Journal, EMBO Press, 2007, 26 (5), pp.1292-1302. ⟨10.1038/sj.emboj.7601586⟩. ⟨pasteur-00161615⟩

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