Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity

Hiroyuki Hosokawa, Tomoaki Tanaka, Yutaka Suzuki, Chiaki Iwamura, Shuichi Ohkubo, Kanji Endoh, Miki Kato, Yusuke Endo, Atsushi Onodera, Damon John Tumes, Akinori Kanai, Sumio Sugano, Toshinori Nakayama

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naïve CD4 T cells into T helper 2 (Th2) cells. However, it is unknown how Gata3 simultaneously activates Th2-specific genes while repressing those of other Th lineages. Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFN-γ. We define a Gata3/Chd4/p300 transcriptional activation complex at the Th2 cytokine loci and a Gata3/Chd4-nucleosome remodeling histone deacetylase repression complex at the Tbx21 locus in Th2 cells. We also demonstrate a physiological role for Chd4 in Th2-dependent inflammation in an in vivo model of asthmatic inflammation. Thus, Gata3/Chd4 forms functionally distinct complexes, which mediate both positive and negative gene regulation to facilitate Th2 cell differentiation.

Original languageEnglish
Pages (from-to)4691-4696
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number12
DOIs
Publication statusPublished - 19 Mar 2013

Keywords

  • T helper 2 cell differentiation
  • Transcriptional regulation

ASJC Scopus subject areas

  • General

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