Genome-wide mapping of histone modification H3K4me3 in bovine oocytes and early embryos

Abstract

Reprogramming of histone modifications is critical to safeguard correct gene expression profile during preimplantation development. Of interest, trimethylation of lysine 4 on histone 3 (H3K4me3) exhibits a unique and dynamic landscape with a potential species-specific feature. Here, we address how it is reprogrammed and its functional significance during oocyte maturation and early embryonic development in cows. Notably, the overall signal of H3K4me3 decreased sharply during embryonic genome activation (EGA). By using low input ChIP-seq technology, we find widespread broad H3K4me3 domains in oocytes and early cleaved embryos. The broad domains are gradually removed after fertilization, which is obviously seen during EGA. Meanwhile, H3K4me3 become enriched at promoter regions. Interestingly, the gene expression level displays a positive correlation with the relative H3K4me3 signal of their promoters when embryos reach 16-cell stage. Importantly, disruption of H3K4me3 demethylases KDM5A-5C increases H3K4me3 level, decreases the embryonic developmental rate and results in dysregulation of over a thousand genes. Meanwhile, KDM5 deficiency causes a re-destribution of H3K4me3 across genome. In particular, the positive correlation between promoter H3K4me3 enrichment and gene expression level disappear. Overall, we describe the genomic reprogramming of H3K4me3 in a greater resolution during bovine preimplantation development and propose that KDM5-mediated re-distribution of H3K4me3 plays an important role in modulating oocyte-to-embryonic transition.