title: Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity.
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.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Chiaki
authors.initials: C
authors.lastname: Iwamura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohkubo
authors.forename: Kanji
authors.initials: K
authors.lastname: Endoh
authors.forename: Miki
authors.initials: M
authors.lastname: Kato
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Endo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Onodera
authors.forename: Damon John
authors.initials: DJ
authors.lastname: Tumes
authors.forename: Akinori
authors.initials: A
authors.lastname: Kanai
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology*; D056426:Genetic Loci / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology*; D009707:Nucleosomes / Q000235:genetics / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D046912:Multiprotein Complexes; D009707:Nucleosomes; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma; C509277:Mi-2beta protein, mouse; D004265:DNA Helicases