The Histone Acetyltransferase Gcn5 Positively Regulates T Cell Activation.

Histone acetyltransferases (HATs) regulate inducible transcription in multiple cellular processes and during inflammatory and immune response. However, the functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily conserved HAT from yeast to human, in immune regulation remain unappreciated. In this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene) specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and demonstrated that Gcn5 plays important roles in multiple stages of T cell functions including development, clonal expansion, and differentiation. Loss of Gcn5 functions impaired T cell proliferation, IL-2 production, and Th1/Th17, but not Th2 and regulatory T cell differentiation. Gcn5 is recruited onto the il-2 promoter by interacting with the NFAT in T cells upon TCR stimulation. Interestingly, instead of directly acetylating NFAT, Gcn5 catalyzes histone H3 lysine H9 acetylation to promote IL-2 production. T cell-specific suppression of Gcn5 partially protected mice from myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, an experimental model for human multiple sclerosis. Our study reveals previously unknown physiological functions for Gcn5 and a molecular mechanism underlying these functions in regulating T cell immunity. Hence Gcn5 may be an important new target for autoimmune disease therapy. Copyright © 2017 by The American Association of Immunologists, Inc.

Citation

Beixue Gao, Qingfei Kong, Yana Zhang, Chawon Yun, Sharon Y R Dent, Jianxun Song, Donna D Zhang, Yiming Wang, Xuemei Li, Deyu Fang. The Histone Acetyltransferase Gcn5 Positively Regulates T Cell Activation. Journal of immunology (Baltimore, Md. : 1950). 2017 May 15;198(10):3927-3938

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PMID: 28424240

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