H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos

ABSTRACT: Parental epigenomes are established during gametogenesis. While they are largely reset soon after fertilization in mammals, maternal histone H3 tri-methylation at lysine 27 (H3K27me3) is inherited by the next generation embryos. How H3K27me3 is properly established in oocytes and passed on to the embryos remains elusive. Furthermore, although polycomb repressive complex 2 (PRC2)-mediated H3K27me3 is known to interplay with PRC1-mediated mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub1) to coordinate repressive polycomb domains in embryonic stem cells (ESCs), how they act in vivo remains unknown. To address these questions, here we profiled H2AK119ub1 dynamics during mouse oogenesis and preimplantation development, and investigated its functions in maternal inheritance of H3K27me3. Integrative analyses with H3K27me3 dynamics revealed that an unusually broad and distal-rich distribution of H2AK119ub1 is established during oogenesis and co-transmitted to embryos together with H3K27me3. On the other hand, an ESC-like canonical distribution of H2AK119ub1 is newly established at the 2-cell stage, a few days earlier than that of H3K27me3. Deficiency in polycomb group ring finger 1 (PCGF1) and PCGF6, essential components of variant PRC1 (vPRC1), leads to massive reduction of H2AK119ub1 and gene-selective loss of H3K27me3 in oocytes. The gene-selective deficient state of H3K27me3 is irreversibly inherited by embryos, which causes bi-allelic expression of H3K27me3-dependent imprinted genes, including Xist, embryonic sublethality, and placental enlargement at term. Collectively, our study not only revealed instructive in vivo dynamics of H2AK119ub1 for H3K27me3 establishment at the maternal-to-embryonic transition, but also identified PCGF1/6-PRC1 as an essential player for intergenerational epigenetic inheritance.

ORGANISM(S): Mus musculus

PROVIDER: GSE153496 | GEO | 2021/01/31

REPOSITORIES: GEO