Resetting of H3K4me2 during mammalian parental-to-zygote transition

Abstract

Upon sperm and oocyte fertilization, drastic histone modification reprograming occurs during preimplantation development. However, the global H3K4me2 landscape and its dynamics reprogramming in this period remains largely unknown. Herein we investigate 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) for histone modification with high-throughput sequencing. We find H3K4me2 extensively exists as a non-canonical pattern in mouse GV oocytes and early embryos. Interestingly, H3K4me2 is erased in MII oocyte and re-established in late 2-cell stage. Importantly, mouse embryos acquire widespread H3K4me2 in CpG-rich and hypomethylated regulatory regions in 4-cell stage, as well as 8-cell stage, but drastic changes happen upon ICM, these CpG-rich H3K4me2 regulatory regions then resolve to either active or repressed states. In summary, our study not only unveil that H3K4me2 transition from parental to zygote, but also provide a H3K4me2 profile during early embryo development, and this will enhance our comprehension to epigenetic reprogramming during mouse early development and in vitro fertilization.