Mammalian embryogenesis involves intricate epigenetic reprogramming and chromatin remodeling. In this study, we investigated the role of BRG1, an ATPase subunit of the SWI/SNF complex, in early embryonic development and mouse embryonic stem cells (mESCs). By generating Brg1 knockout oocytes and mESCs, we found that BRG1 deficiency led to multiple defects. In mouse early embryos, maternal knockout of Brg1 resulted in impaired blastocyst formation, delayed embryo development and dysregulated expression of zygotic genome activation (ZGA) genes. A contributing factor is aberrant nucleosome positioning that sterically hinders access of totipotency-related transcription factors (TFs) to key regulatory loci. In mESCs, Brg1 knockout resulted in abnormal colony morphology, decreased pluripotency marker expression, and reduced cell proliferation. BRG1 regulated pluripotency mainly by influencing the binding of pluripotency-related TFs, such as OCT4, at enhancers by modulating chromatin accessibility. We found that the impact of BRG1 on transcription factor occupancy is dependent on cellular identity. Therefore, we identified embryo/ESC-specific BRG1-dependent TFs, which may be functionally implicated in the governance of totipotent and pluripotent states. Our study revealed that BRG1-mediated reorganization of promoter/enhancer nucleosome architecture directs the recruitment of cell type-specific transcriptional regulators essential for sustaining pluripotent and totipotent cell identities.
Shi et al. (Sun,) studied this question.
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