The chromatin remodeler Chd4 maintains embryonic stem cell identity by controlling pluripotency- and differentiation-associated genes.

摘要: The unique properties of embryonic stem cells (ESCs), including unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic epigenetic networks composed transcriptional factors modulators. However, the molecular mechanisms underlying function these regulators not fully elucidated. Chromodomain helicase DNA-binding protein 4 (Chd4), an ATPase subunit nucleosome remodeling deacetylase (NuRD) complex, is highly expressed in ESCs. its ESC regulation remains elusive. Here we report that Chd4 required for maintenance self-renewal. RNAi-mediated silencing disrupted up-regulated lineage commitment-associated genes under culture conditions. During embryoid body formation, observed significantly stronger induction differentiation-associated Chd4-deficient cells. phenotype was different from caused deletion Mbd3, another NuRD complex. Transcriptomic analyses revealed secured identity controlling expression subsets pluripotency- genes. Importantly, repressed transcription T box 3 (Tbx3), a factor with important functions fate determination. Tbx3 knockdown partially rescued aberrant activation genes, especially endoderm-associated induced depletion. Moreover, identified interaction histone variant H2A.Z. This stabilized inhibiting degradation through ubiquitin-proteasome pathway. Collectively, this study identifies Chd4-Tbx3 axis role H2A.Z maintaining stability proteins.