The remodeling of bivalent chromatin is essential for mouse peri-implantation embryogenesis [CUT&Tag]

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. For embryo samples, we generated complete knockouts of each factor using the C-CRISPR approach or treated E3.5 blastocysts with 50μM GSK-J4. We cultured treated embryos through the peri-implantation period. At the E5.0 stage, we performed H3K27me3 profiling on the EPI of each treated embryo using CUT&Tag to assess gene perturbation.