| Polycomb group(Pc G)is a family of crucial regulators first discovered in Drosophila that can play important roles in chromatin remodeling and transcriptional silencing.Pc G proteins can form Polycomb Repressive Complex 1(PRC1)and 2(PRC2),which can catalyze the histone modification H2AK119ub1 and H3K27me3,respectively.The two intimately associated histone modifications play central roles in Pc G-mediated transcriptional repression and are of paramount importance to mammalian development.In somatic cells and embryonic stem cells,PRC1/H2AK119ub1 and PRC2/H3K27me3 have been reported to largely overlap in the genome,particularly at canonical Pc G targets(i.e.,the bivalent promoters of developmental genes)due to the mutual recruitment activity of these two associated complexes.In addition to decorating canonical Pc G targets,H3K27me3 has also been reported to form broad distal domains with low DNA methylation levels in mouse oocytes,which are inherited by early embryos to mediate DNA methylation-independent non-canonical imprinting.Due to technical challenges,it is still difficult to obtain the whole genome-wide map of H2AK119ub1 modification in early embryos.Therefore,the distribution of H2AK119ub1 in early embryos and whether H2AK119ub1 and H3K27me3 can function independently in different genomic regions are still not clear.Here,we developed an ultra-sensitive chromatin immunoprecipitation sequencing(Ch IP-Seq)method termed CATCH-Seq(carrier DNA assisted Ch IP-Seq)and generated allelic H2AK119ub1 profiles in mouse gametes and early embryos.Comparative analysis showed similar distributions of H2AK119ub1 and H3K27me3 in the gametes,although there are more H2AK119ub1 enriched regions.However,in early embryonic development after fertilization,the two modifications show an unexpected genomewide decoupling.In early embryos,H2AK119ub1 but not H3K27me3 is enriched at canonical Pc G targets,and H3K27me3 is only associated with broad distal domains and non-canonical imprinting regions,indicating that H2AK119ub1 represses future bivalent genes without H3K27me3,but is not required for the maintenance of DNA methylation-independent but H3K27me3-dependent non-canonical imprinting.Maternal-to-zygotic transition(MZT)is a crucial process in embryonic development,in which the maternal m RNA and proteins maintaining early development are degraded,and the zygotic genome activation(ZGA)takes place.ZGA is an important event in early embryonic development and correct ZGA is necessary for normal development.In mouse early embryonic development,we found that H2AK119ub1 but not H3K27me3 at the promoters of ZGA genes underwent drastic reprogramming,suggesting that the deubiquitination of H2AK119ub1 may be related to the normal ZGA.Consistent with this observation,ZGA is compromised by the deletion of the deubiquitinase USP16.In conclusion,H2AK119ub1 and H3K27me3 histone modifications have different and independent distribution and functions in mouse early embryonic development,and H2AK119ub1 may play a more important role both in the silencing of bivalent developmental genes in absence of H3K27me3 and the ZGA process.Our study sheds light on the reprogramming of H2AK119ub1 modification in gametes and early embryonic development,and reveals the different distribution and functions of H2AK119ub1 and H3K27me3 modifications in early embryos,and further explores the epigenetic mechanism in mouse early embryos. |
