The Novel Role of in Mammalian Embryonic Genome Activation as an H3K9me3 Modulator.

The changes in epigenetic modifications during early embryonic development significantly impact mammalian embryonic genome activation (EGA) and are species-conserved to some degree. Here, we reanalyzed the published RNA-Seq of human, mouse, and goat early embryos and found that (zinc finger protein 296) expression was higher at the EGA stage than at the oocyte stage in all three species (adjusted -value < 0.05 |log2(foldchange)| ≥ 1). Subsequently, we found that was conserved across human, mouse, goat, sheep, pig, and bovine embryos. In addition, we identified that ZFP296 interacts with the epigenetic regulators KDM5B, SMARCA4, DNMT1, DNMT3B, HP1β, and UHRF1. The Cys-His(C2H2) zinc finger domain TYPE2 TYPE3 domains of ZFP296 co-regulated the modification level of the trimethylation of lysine 9 on the histone H3 protein subunit (H3K9me3). According to ChIP-seq analysis, ZFP296 was also enriched in , , , , and in the mESC genome. Then, knockdown of the expression of at the late zygote of the mouse led to the early developmental arrest of the mouse embryos and failure resulting from a decrease in H3K9me3. Together, our results reveal that is an H3K9me3 modulator which is essential to the embryonic genome activation of mouse embryos.