Transcription factor-dependent chromatin remodeling of il18r1 during Th1 and Th2 differentiation

Qing Yu, Hua Chen Chang, Ayele Nati N. Ahyi, Mark H. Kaplan

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The IL-18Rα-chain is expressed on Th1 but not Th2 cells. We have recently shown that Stat4 is an important component of programming the Il18r1 locus (encoding IL-18Rα) for maximal expression in Th1 cells. Il18r1 is reciprocally repressed during Th2 development. In this report, we demonstrate the establishment of DH patterns that are distinct among undifferentiated CD4 T, Th1, and Th2 cells. Stat6 is required for the repression of Il18r1 expression and in Stat6-deficient Th2 cultures, mRNA levels, histone acetylation, and H3K4 methylation levels are intermediate between levels observed in Th1 and Th2 cells. Despite the repressive effects of IL-4 during Th2 differentiation, we observed only modest binding of Stat6 to the Il18r1 locus. In contrast, we observed robust GATA-3 binding to a central region of the locus where DNase hypersensitivity sites overlapped with conserved non-coding sequences in Il18r1 introns. Ectopic expression of GATA-3 in differentiated Th1 cells repressed Il18r1 mRNA and surface expression of IL-18Rα. These data provide further mechanistic insight into transcription factor-dependent establishment of Th subset-specific patterns of gene expression.

Original languageEnglish (US)
Pages (from-to)3346-3352
Number of pages7
JournalJournal of Immunology
Volume181
Issue number5
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Transcription factor-dependent chromatin remodeling of il18r1 during Th1 and Th2 differentiation'. Together they form a unique fingerprint.

  • Cite this