Methylation of Gata3 protein at Arg-261 regulates transactivation of the Il5 gene in T helper 2 cells
Date
2015
Authors
Hosokawa, H.
Kato, M.
Tohyama, H.
Tamaki, Y.
Endo, Y.
Kimura, M.Y.
Tumes, D.J.
Motohashi, S.
Matsumoto, M.
Nakayama, K.I.
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Journal article
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Journal of Biological Chemistry, 2015; 290(21):13095-13103
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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 inter-leukin- 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 methyla-tion- 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.
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Copyright 2015 The American Society for Biochemistry and Molecular Biology (https://creativecommons.org/licenses/by/4.0/)
Access Condition Notes: This is an open access article