The remodeling of bivalent chromatin is essential for mouse peri-implantation embryogenesis [mESC valid]

Since its discovered, the dynamics and molecular regulation of bivalent chromatin during early embryogenesis remain poorly understood. We trace gene expression and bivalent chromatin dynamics in peri-implantation mouse embryogenesis, showing bifurcated establishment in epiblast and primitive endoderm. We identify transiently maintained bivalent domains (TB domains) in the epiblast, crucial for pluripotency progression. Our study reveals 22 candidate factors, including ZBTB17, essential for resolving TB domains and activating pluripotency regulators. These dynamics are conserved in human pluripotent transition. Overall design: We generated a naïve Zbtb17^dTAG/dTAG ESC line with an endogenous 3×HA tag and performed 2i ESC-to-EpiLC pluripotency transition assays, which recapitulate the transition from naïve to formative pluripotency, followed by the collection of transcriptomic and histone modification data, as well as ZBTB17 and EED binding profiles. To directly validate the bivalent chromatin status of the TB and CB gene sets, we performed sequential ChIP-seq (reChIP-seq) in naïve ESCs and EpiLCs, which serve as in vitro models of the peri-implantation epiblast.