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

Hiroyuki Hosokawa, Miki Kato, Hiroyuki Tohyama, Yuuki Tamaki, Yusuke Endo, Motoko Y. Kimura, Damon John Tumes, Shinichiro Motohashi, Masaki Matsumoto, Keiichi I. Nakayama, Tomoaki Tanaka, Toshinori Nakayama

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)13095-13103
Number of pages9
JournalJournal of Biological Chemistry
Volume290
Issue number21
DOIs
Publication statusPublished - May 22 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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