Methylation of Gata3 at Arg261 regulates transactivation of the Il5 gene in T helper 2 cells [Gene Regulation]

April 10th, 2015 by Hosokawa, H., Kato, M., Tohyama, H., Tamaki, Y., Endo, Y., Kimura, M. Y., Tumes, D. J., Motohashi, S., Matsumoto, M., Nakayama, K. I., Tanaka, T., Nakayama, T.

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 Arg261 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 IFN╬│ 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.