ERK1/2 Activities Are Dispensable for Oocyte Growth but Are Required for Meiotic Maturation and Pronuclear Formation in Mouse

Previous studies revealed that extracellular regulated kinase-1 and -2 （ERK1/2） cascade plays pivotal roles in regulating oocyte meiotic cell cycle progression. However, most knowledge about the in vivo function of ERK1/2 in mammalian oocytes was indirectly obtained from analyzing the phenotypes of Mos knockout mice. In this study, we knocked out Erkl and Erk2 in mouse oocytes as early as the primordial follicle stage using the well-characterized Gdp-Cre mouse model, and for the first time directly investigated the in vivo function of ERK1/2 in mouse oocytes. In this novel mouse model, we observed that ERK1/2 activities in oocyte are dispensable for primordial follicle maintenance, activation and follicle growth. Different from the Mos null oocytes, the ERK1/2-deleted oocytes had well-assembled spindles at metaphase I （MI）, extruded polar body-I （PB1） with normal sizes, and did not undergo a full parthenogenetic activation characterized for pronuclear formation. However, the ovulated ERK1/2-deleted oocytes had poorly-assembled metaphase II （MII） spindles, spontaneously released polar body-2 （PB2）, and were arrested at another metaphase called metaphase III （MIII）. In addition, ERK1/2 deletion prevented male pronuclear formation after fertilization, and caused female infertility. In conclusion, these results indicate that ERK1/2 activities are required for not only MII-arrest maintenance, but also efficient pronuclear formation in mouse oocytes.

Genomewide decoupling of H2AK119ub1 and H3K27me3 in early mouse development

Polycomb group(Pc G)proteins are crucial chromatin regulators during development.H2 AK119 ub1(H2 Aub)and H3 K27 me3 are catalyzed by Polycomb-repressive complex 1 and 2(PRC1/2)respectively,and they largely overlap in the genome due to mutual recruitment of the two complexes.However,it is unclear whether PRC1/H2 Aub and PRC2/H3 K27 me3 can also function independently.By developing an ultra-sensitive carrier-DNA-assisted chromatin immunoprecipitation sequencing method termed CATCH-Seq,we generated allelic H2 Aub profiles in mouse gametes and early embryos.Our results revealed an unexpected genomewide decoupling of H2 Aub and H3 K27 me3 in mouse preimplantation embryos,where H2 Aub but not H3 K27 me3 was enriched at Pc G targets while only H3 K27 me3 was deposited in the broad distal domains associated with DNA methylation-independent non-canonical imprinting.These observations suggest that H2 Aub represses future bivalent genes during early embryogenesis without H3 K27 me3,but it is not required for the maintenance of non-canonical imprinting,which is mediated by maternal H3 K27 me3.Thus,our study reveals the distinct depositions and independent functions of H2 Aub and H3 K27 me3 during early mammalian development.