Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2008-06-14Keywords
AnimalsCD4-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
Metadata
Show full item recordAbstract
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.Source
Immunity. 2008 Jun;28(6):763-73. Link to article on publisher's site
DOI
10.1016/j.immuni.2008.04.016Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39225PubMed ID
18549798Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.immuni.2008.04.016