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Chromatin Immunoprecipitation (ChIP) to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells
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Published on: July 29, 2010

Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation

Min Shi1, Tsung H Lin, Kenneth C Appell

  • 1Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Immunity
|June 14, 2008
PubMed

Differentiation of naive CD4+ T cells into T helper type 1 (Th1) effector cells requires both T cell receptor (TCR) signaling and cytokines such as interleukin-12 and interferon gamma (IFN-gamma). Here, we report that a third cytokine signal, mediated by the Janus family tyrosine kinase 3 (Jak3) and signal transducer and activator of transcription 5 (STAT5) pathway, is also required for Th1 cell differentiation. In the absence of Jak3-dependent signals, naive CD4+ T cells proliferate robustly but produce little IFN-gamma after Th1 cell polarization in vitro. This defect is not due to reduced activation of STAT1 or STAT4 or to impaired upregulation of the transcription factor T-bet. Instead, we find that T-bet binding to the Ifng promoter is greatly diminished in the absence of Jak3-dependent signals, correlating with a decrease in Ifng promoter accessibility and histone acetylation. These data indicate that Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 cell differentiation.

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