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J Biol Chem. 2015 May 22;290(21):13095-103. doi: 10.1074/jbc.M114.621524. Epub 2015 Apr 10.

Methylation of Gata3 protein at Arg-261 regulates transactivation of the Il5 gene in T helper 2 cells.

Author information

1
From the Department of Immunology.
2
Department of Medical Immunology.
3
the Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, and.
4
Department of Clinical Cell Biology, and Division of Endocrinology and Metabolism, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, CREST, Japan Science and Technology Agency, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
5
From the Department of Immunology, CREST, Japan Science and Technology Agency, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan tnakayama@faculty.chiba-u.jp.

Abstract

Gata3 acts as a master regulator for T helper 2 (Th2) cell differentiation by inducing chromatin remodeling of the Th2 cytokine loci, accelerating Th2 cell proliferation, and repressing Th1 cell differentiation. Gata3 also directly transactivates the interleukin-5 (Il5) gene via additional mechanisms that have not been fully elucidated. We herein identified a mechanism whereby the methylation of Gata3 at Arg-261 regulates the transcriptional activation of the Il5 gene in Th2 cells. Although the methylation-mimicking Gata3 mutant retained the ability to induce IL-4 and repress IFNγ production, the IL-5 production was selectively impaired. We also demonstrated that heat shock protein (Hsp) 60 strongly associates with the methylation-mimicking Gata3 mutant and negatively regulates elongation of the Il5 transcript by RNA polymerase II. Thus, arginine methylation appears to play a pivotal role in the organization of Gata3 complexes and the target gene specificity of Gata3.

KEYWORDS:

GATA transcription factor; Gata3; Hsp60; IL-5; T helper cells; Th2; post-translational modification (PTM); protein methylation; transcription factor

PMID:
25861992
PMCID:
PMC4505565
DOI:
10.1074/jbc.M114.621524
[Indexed for MEDLINE]
Free PMC Article

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