STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus

Audrey O'Sullivan, Hua Chen Chang, Qing Yu, Mark H. Kaplan

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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 α 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.

Original languageEnglish (US)
Pages (from-to)7339-7345
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number8
DOIs
StatePublished - Feb 20 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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