The histone acetyltransferase Gcn5 positively regulates T Cell activation

Beixue Gao, Qingfei Kong, Yana Zhang, Chawon Yun, Sharon Y.R. Dent, Jianxun Song, Donna Zhang, Yiming Wang, Xuemei Li, Deyu Fang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3927-3938
Number of pages12
JournalJournal of Immunology
Volume198
Issue number10
DOIs
StatePublished - May 15 2017

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Histone Acetyltransferases
T-Lymphocytes
Proteins
Interleukin-2
Autoimmune Experimental Encephalomyelitis
Regulatory T-Lymphocytes
Acetylation
Histones
Autoimmune Diseases
Lysine
Multiple Sclerosis
Cell Differentiation
Immunity
Theoretical Models
Yeasts
Cell Proliferation

ASJC Scopus subject areas

  • Immunology

Cite this

Gao, B., Kong, Q., Zhang, Y., Yun, C., Dent, S. Y. R., Song, J., ... Fang, D. (2017). The histone acetyltransferase Gcn5 positively regulates T Cell activation. Journal of Immunology, 198(10), 3927-3938. https://doi.org/10.4049/jimmunol.1600312

The histone acetyltransferase Gcn5 positively regulates T Cell activation. / Gao, Beixue; Kong, Qingfei; Zhang, Yana; Yun, Chawon; Dent, Sharon Y.R.; Song, Jianxun; Zhang, Donna; Wang, Yiming; Li, Xuemei; Fang, Deyu.

In: Journal of Immunology, Vol. 198, No. 10, 15.05.2017, p. 3927-3938.

Research output: Contribution to journalArticle

Gao, B, Kong, Q, Zhang, Y, Yun, C, Dent, SYR, Song, J, Zhang, D, Wang, Y, Li, X & Fang, D 2017, 'The histone acetyltransferase Gcn5 positively regulates T Cell activation', Journal of Immunology, vol. 198, no. 10, pp. 3927-3938. https://doi.org/10.4049/jimmunol.1600312
Gao B, Kong Q, Zhang Y, Yun C, Dent SYR, Song J et al. The histone acetyltransferase Gcn5 positively regulates T Cell activation. Journal of Immunology. 2017 May 15;198(10):3927-3938. https://doi.org/10.4049/jimmunol.1600312
Gao, Beixue ; Kong, Qingfei ; Zhang, Yana ; Yun, Chawon ; Dent, Sharon Y.R. ; Song, Jianxun ; Zhang, Donna ; Wang, Yiming ; Li, Xuemei ; Fang, Deyu. / The histone acetyltransferase Gcn5 positively regulates T Cell activation. In: Journal of Immunology. 2017 ; Vol. 198, No. 10. pp. 3927-3938.
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