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Bcl11b- and GATA3-mediated gene regulation in Th2 cells

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE109107 | GEO | 2018/03/05

REPOSITORIES: GEO

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