Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation
Department of Pathology
Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; *Chromatin Assembly and Disassembly; Cytokines; Epigenesis, Genetic; Interferon-gamma; Janus Kinase 3; Mice; Mice, Mutant Strains; Promoter Regions, Genetic; STAT Transcription Factors; STAT5 Transcription Factor; Signal Transduction; Th1 Cells
Life Sciences | Medicine and Health Sciences
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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Citation: Immunity. 2008 Jun;28(6):763-73. Link to article on publisher's site
DOI of Published Version
Shi, Min; Lin, Tsung H.; Appell, Kenneth C.; and Berg, Leslie J., "Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation" (2008). Open Access Articles. 2030.