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IFN-? 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-? 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-? can suppress permissive chromatin remodeling of regulatory region of the Il4 gene. We demonstrate that IFN-? suppresses H3K4 dimethylation at the intronic enhancer region of the Il4 gene. The IFN-?-mediated suppression of permissive chromatin remodeling is IFN-? receptor-, STAT1-, and T-bet-dependent. Our study reveals a novel mechanism of how Th1 cells silence the Il4 gene.

SUBMITTER: Nishida J

PROVIDER: S-EPMC3615094 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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IFN-γ suppresses permissive chromatin remodeling in the regulatory region of the Il4 gene.

Nishida Jun J Li Yapeng Y Zhuang Yonghua Y Huang Zan Z Huang Hua H

Cytokine 20130313 1

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 intro ...[more]

PMID: 23490416

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Project description:BackgroundATP-dependent chromatin remodelers are evolutionarily conserved complexes that alter nucleosome positioning to influence many DNA-templated processes, such as replication, repair, and transcription. In particular, chromatin remodeling can dynamically regulate gene expression by altering accessibility of chromatin to transcription factors.Scope of reviewThis review provides an overview of the importance of chromatin remodelers in the regulation of metabolic gene expression. Particular emphasis is placed on the INO80 and SWI/SNF (BAF/PBAF) chromatin remodelers in both yeast and mammals. This review details discoveries from the initial identification of chromatin remodelers in Saccharomyces cerevisiae to recent discoveries in the metabolic requirements of developing embryonic tissues in mammals.Major conclusionsINO80 and SWI/SNF (BAF/PBAF) chromatin remodelers regulate the expression of energy metabolism pathways in S. cerevisiae and mammals in response to diverse nutrient environments. In particular, the INO80 complex organizes the temporal expression of gene expression in the metabolically synchronized S. cerevisiae system. INO80-mediated chromatin remodeling is also needed to constrain cell division during metabolically favorable conditions. Conversely, the BAF/PBAF remodeler regulates tissue-specific glycolytic metabolism and is disrupted in cancers that are dependent on glycolysis for proliferation. The role of chromatin remodeling in metabolic gene expression is downstream of the metabolic signaling pathways, such as the TOR pathway, a critical regulator of metabolic homeostasis. Furthermore, the INO80 and BAF/PBAF chromatin remodelers have both been shown to regulate heart development, the tissues of which have unique requirements for energy metabolism during development. Collectively, these results demonstrate that chromatin remodelers communicate metabolic status to chromatin and are a central component of homeostasis pathways that optimize cell fitness, organismal development, and prevent disease.

Dataset Information

IFN-? suppresses permissive chromatin remodeling in the regulatory region of the Il4 gene.

Publications

IFN-γ suppresses permissive chromatin remodeling in the regulatory region of the Il4 gene.

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