Resetting of H3K4me2 during mammalian parental-to-zygote transition

Upon sperm and oocyte fertilization, the embryo undergoes drastic histone modification reprogramming during pre-implantation development. In this study, we investigated the erasure and re-establishment of H3K4me2 in mouse GV, MII, and embryos using an improved approach called Cleavage Under Targets and Release Using Nuclease (CUT&RUN) with high-throughput sequencing. We found that H3K4me2 extensively occurs as a non-canonical pattern in mouse GV oocytes and early embryos, and parental H3K4me2 was erased by maternal LSD2 during forming the pronucleus in the zygote. The H3K4me2 was erased from GV to MII oocyte and was re-established in the late two-cell stage, removing this epigenetic burden is crucial for ZGA. We then revealed the H3K4me2 locates widespread in the CpG-rich and hypomethylated regulatory regions in the four-cell stage, and the eight-cell stage, but dramatic changes occurred in the inner cell mass (ICM) in mouse embryos. Then, these CpG-rich H3K4me2 regulatory regions became either activated or repressed. To summarize, in this study, we elucidated the pattern of H3K4me2 transition from parent to zygote and H3K4me2 profile during early embryo development. Our findings might provide deeper insights into epigenetic reprogramming during early development and in vitro fertilization in mammalian.