Journal
EMBO JOURNAL
Volume 26, Issue 5, Pages 1292-1302Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.emboj.7601586
Keywords
BRG1; chromatin remodeling; interleukin-12; STAT4; Th1 cell differentiation
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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-12R beta 2, and are therefore unresponsive to IL-12. We have examined the mechanisms that control Th1-specific expression of the human IL-12R beta 2 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-12R beta 2 regulatory regions and was associated with lowlevel gene transcription at the IL-12R beta 2 locus. However, high-level IL-12R beta 2 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-12R beta 2 expression during Th1 cell development.
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