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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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

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Th1 Cells
Chromatin Assembly and Disassembly
Th2 Cells
Transcription Factors
Messenger RNA
Deoxyribonucleases
Acetylation
Interleukin-4
Histones
Introns
Methylation
Hypersensitivity
T-Lymphocytes
Gene Expression

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Transcription factor-dependent chromatin remodeling of il18r1 during Th1 and Th2 differentiation. / Yu, Qing; Chang, Hua Chen; Ahyi, Ayele Nati N; Kaplan, Mark.

In: Journal of Immunology, Vol. 181, No. 5, 01.09.2008, p. 3346-3352.

Research output: Contribution to journalArticle

Yu, Qing ; Chang, Hua Chen ; Ahyi, Ayele Nati N ; Kaplan, Mark. / Transcription factor-dependent chromatin remodeling of il18r1 during Th1 and Th2 differentiation. In: Journal of Immunology. 2008 ; Vol. 181, No. 5. pp. 3346-3352.
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