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Publication : STAT4 is required for interleukin-12-induced chromatin remodeling of the CD25 locus.

First Author  O'Sullivan A Year  2004
Journal  J Biol Chem Volume  279
Issue  8 Pages  7339-45
PubMed ID  14660657 Mgi Jnum  J:88966
Mgi Id  MGI:3037517 Doi  10.1074/jbc.M309979200
Citation  O'Sullivan A, et al. (2004) STAT4 is required for interleukin-12-induced chromatin remodeling of the CD25 locus. J Biol Chem 279(8):7339-45
abstractText  Signal transducer and activator of transcription 4 (STAT4) is a critical mediator of interleukin-12 (IL-12)-stimulated inflammatory immune responses. Despite extensive analysis of the immune responses of STAT4-deficient mice, there is still very little understood about STAT4-dependent gene induction. IL-12 stimulated increases in IL-2 receptor alpha chain gene (CD25) mRNA levels and surface expression require STAT4. In this report, we utilize chromatin immunoprecipitation assays to analyze IL-12-stimulated and STAT4-dependent changes in chromatin remodeling of the CD25 gene. Gene activation requires binding of STAT4 to the PRRIII upstream regulatory element, the recruitment of the CREB-binding protein (CBP), and chromatin remodeling including increased acetylation and decreased methylation of histones within the CD25 promoter. Evidence suggests that STAT4 also facilitates binding of other factors to the CD25 promoter including c-Jun. Thus, these results provide a model for STAT4-dependent gene induction and a mechanism for cytokine-induced expression of the CD25 gene.
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