FIGURE 6.

Methylated Gata3 has a dominant-negative effect on the Gata3-mediated transactivation of the Il5 gene. A, schematic representation of Gata3-mediated transactivation of the Il5 gene in resting and TCR-reactivated Th2 cells. In resting Th2 cells, methylated Gata3 binds to the Il5 promoter with Hsp60 (upper). After TCR restimulation (TCR stim.), AP-1 and Ets1 are activated and organize the complex with Gata3 at the Il5 locus. Demethylation of Gata3 can be induced by unknown mechanisms resulting in the dissociation of Hsp60 from Gata3 complex, leading to the Il5 transcription (lower). NFAT, nuclear factor of activated T-cells; RNA pol II, RNA polymerase II; S5p, phospho-Ser-5; S2p, phospho-Ser-2. B, naive CD4 T cells from C57BL/6 mice were stimulated under Th2 conditions and then infected with a retrovirus vector carrying WT or mutant Gata3 cDNAs. Four days later, the cells were restimulated and subjected to IL-4, IL-5, IL-13, and IFNγ staining, followed by a FACS analysis.