GSE108633
Bcl11b, a Novel GATA3-Interacting Protein, Suppresses Th1 while Limiting Th2 Cell Differentiation (H3K27ac and DNase-Seq)
GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we report that the transcription factor B cell lymphoma 11b (Bcl11b), a previously unknown component of GATA3 transcriptional complex, is involved in GATA3-mediated gene regulation. Bcl11b binds to GATA3 through protein-protein interaction, and they co-localize at many important cis-regulatory elements in Th2 cells. The expression of type 2 cytokines, including IL-4, IL-5 and IL-13, is up-regulated in Bcl11b-deficient Th2 cells both in vitro and in vivo; such up-regulation is completely GATA3-dependent. Genome-wide analyses of Bcl11b- and GATA3-regulated gene (from RNA-Seq), co-binding pattern (from ChIP-Seq), and Bcl11b-mediated epigenetic changes (in H3K27ac and DHSs) suggest that GATA3/Bcl11b complex is involved in limiting Th2 gene expression, as well as in inhibiting non-Th2 gene expression. Thus, Bcl11b controls both GATA3-mediated gene activation and repression in Th2 cells. Overall design: Naïve CD4 T cells were isolated from Bcl11bfl/fl-CreERT2 mice and cultured under Th2 conditions with or without 4-OHT for 4 days (early Th2 cells). Naïve CD4 T cells were isolated from Bcl11bfl/fl-CreERT2 mice and cultured under Th2 conditions for 4 days. Then, after resting in IL-2-containing medium for one day, the primed cells were further cultured under Th2 conditions with or without 4-OHT for 4 days (late Th2 cells). ChIP-Seq of histone modification H3K27ac and scDNase-Seq analysis in early and late WT or KO Th2 cells.