The remodeling of bivalent chromatin is essential for mouse peri-implantation embryogenesis [Wild type RNA-Seq]

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 isolated specific lineages at consecutive time points using well-established in vitro embryo culture and in vivo dissection techniques. Samples included ICM and TE from E3.5 blastocysts, and EPI and PE from E4.5, E4.75, E5.0, E5.25, and E5.5 embryos. A Pdgfra-promoter-driven EGFP reporter mouse line was employed to facilitate lineage-specific isolation. We performed ultra-low-input chromatin immunoprecipitation sequencing (ULI-NChIP-seq) for H3K4me3 and H3K27me3, Cleavage under targets and tagmentation (Cut&Tag) for Pol II binding, and Smart-seq2 for transcriptome analysis.