title: IFN-γ suppresses permissive chromatin remodeling in the regulatory region of the Il4 gene.
abstract: In order to develop the most effective T helper type-1 (Th1) immunity, naïve CD4(+) T cells must acquire the capacity to express IFN-γ while silencing T helper type-2 (Th2) cytokine-producing potential. An Il4 gene silencer has been described. However, it is not completely understood how the silencer works. In this study, we examine whether IFN-γ can suppress permissive chromatin remodeling of regulatory region of the Il4 gene. We demonstrate that IFN-γ suppresses H3K4 dimethylation at the intronic enhancer region of the Il4 gene. The IFN-γ-mediated suppression of permissive chromatin remodeling is IFN-γ receptor-, STAT1-, and T-bet-dependent. Our study reveals a novel mechanism of how Th1 cells silence the Il4 gene.
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Nishida
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Li
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000187:drug effects; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006657:Histones / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D007438:Introns / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D006657:Histones; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015847:Interleukin-4; D007371:Interferon-gamma; D008239:Lysine