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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2013-03, Vol.110 (12), p.4691-4696
• Main Authors: Hosokawa, Hiroyuki, Tanaka, Tomoaki, Suzuki, Yutaka, Iwamura, Chiaki, Ohkubo, Shuichi, Endoh, Kanji, Kato, Miki, Endo, Yusuke, Onodera, Atsushi, Tumes, Damon John, Kanai, Akinori, Sugano, Sumio, Nakayama, Toshinori
• Format: Article
• Language: English
• Subjects: Animals; Asthma - genetics; Asthma - immunology; Asthma - pathology; Biological Sciences; Cell Differentiation - immunology; Cellular differentiation; Chromatin; Cultured cells; Cytokines; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA Helicases - genetics; DNA Helicases - metabolism; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - immunology; Genes; Genetic loci; Genetic Loci - immunology; Histones; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Interferon-gamma - genetics; Interferon-gamma - immunology; Mice; Mice, Inbred BALB C; Multiprotein Complexes - genetics; Multiprotein Complexes - immunology; Nucleosomes - genetics; Nucleosomes - immunology; Proteins; Renovations; Repression; T cell receptors; T lymphocytes; T-Box Domain Proteins - genetics; T-Box Domain Proteins - immunology; Th2 Cells - immunology; Th2 Cells - pathology; Transcription, Genetic - genetics; Transcription, Genetic - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1220865110

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 Tb×21 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.