SRA

Reprogramming of histone modification regulates gene expression and mammal preimplantation development. Trimethylation of lysine 4 on histone 3 (H3K4me3) has unique landscape in mouse oocytes and early embryos. However, the dynamics and function of H3K4me3 in livestock embryos remain unclear. To address how it is reprogrammed in domestic animals, we profiled changes of H3K4me3 during bovine early embryo development. Notably, the overall signal of H3K4me3 decreased during embryonic genome activation (EGA). By utilizing ultra-low-input native ChIP-seq (ULI-NChIP-seq) technology, we observed widespread broad H3K4me3 domains in oocytes and embryos. The signal of broad H3K4me3 began to decrease after fertilization and was lowest after EGA. Along with the removal of broad H3K4me3, deposition of H3K4me3 at promoter regions enhanced gradually. Besides, the transcriptional activity and signal of promoter H3K4me3 showed positive correlation after the erasure of broad H3K4me3 at 16-cell stage. Moreover, knocking down of demethylases KDM5A, KDM5B and KDM5C caused EGA delay and blastocyst formation failure. RNA-seq analysis revealed 47.8% down-regulated genes in knockdown embryos at 8/16-cell stage were EGA genes, and 63.1% of up-regulated genes were maternal transcripts. Particularly, the positive correlation between transcriptional activity and promoter H3K4me3 during EGA was restrained when knocking down of KDM5A, KDM5B and KDM5C. Overall, our work initiatively mapped the genomic reprogramming of H3K4me3 during bovine preimplantation development, and KDM5A/B/C played roles in modulating oocyte-to-embryonic transition (OET) through timely erasure of broad H3K4me3 domains far away from promoters. Overall design: Examination of H3K4me3 genomic distribution by ULI-NChIP-seq in bovine embryos