Significance GATA-binding protein 3 (Gata3) controls the differentiation of naive CD4 T cells into T helper 2 (Th2) cells by induction of chromatin remodeling at the Th2 cytokine gene loci. Gata3 also facilitates Th2 cell proliferation via unknown mechanisms. We have identified a functional Gata3/RuvB-like protein 2 (Ruvbl2) complex that regulates the proliferation of differentiating Th2 cells through the repression of a CDK inhibitor, cyclin-dependent kinase inhibitor 2c ( Cdkn2c ). Gata3 directly bound to the Cdkn2c locus in an Ruvbl2-dependent manner, and Cdkn2c-knockdown experiments indicated an important role for this molecule in the Gata3-mediated induction of Th2-cell proliferation. Ruvbl2-knockdown Th2 cells showed decreased antigen-induced expansion and caused less airway inflammation in vivo, indicating an important role for Ruvbl2 in Th2 cells in allergic reactions.

Background: Gata3 directly transactivates the Il5 gene. Results: The methylation-mimicking Gata3 mutant at Arg-261 had a selective defect in the induction of IL-5 production via recruitment of Hsp60 to prevent transactivation. Conclusion: Arginine methylation on Gata3 may play a critical role in the organization and function of the Gata3 transcriptional complex. Significance: A new regulatory mechanism of Gata3-mediated Il5 transactivation is revealed.