Functionally distinct Gata3/Chd4 complexes coordinately establish Th2 cell identity. (P1340)

Abstract Gata3 is a GATA family transcription factor that controls differentiation of naïve CD4 T cells into T helper (Th) 2 cells. However, it is unknown how Gata3 simultaneously activates Th2-specific genes while repressing those of other Th lineages. Here we show that Chd4 (chromodomain helicase DNA-binding protein 4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFNγ. We define a Gata3/Chd4/p300 transcriptional activation complex at the Th2 cytokine loci and a Gata3/Chd4-NuRD repression complex at the Tbx21 locus in Th2 cells. We also demonstrated a physiological role for Chd4 in Th2-dependent inflammation in an in vivo model of asthmatic inflammation. Thus, Gata3/Chd4 forms functionally distinct complexes, which mediate both positive and negative gene regulation to facilitate Th2 cell differentiation.