Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation

The maternal-to-zygotic transition (MZT) is underpinned by wide-spread transcriptomic and epigenomic remodeling that facilitates totipotency acquisition. Although the MZT is a universal feature of mammalian preimplantation development, the factors that regulate this transition remain unclear because the timing of embryonic genome activation (EGA) is highly species-specific, suggesting divergence of regulatory circuitry. Indeed, open chromatin during mouse and human EGA shows differential motif enrichment, implicating distinct regulators. To better assess chromatin remodeling during mammalian development, chromatin accessibility was profiled in bovine oocytes and in vitro produced embryos. Accessibility that was established pre-EGA marked maternal factor recognition sites, i.e. CTCF, KLFs, NFY, and SP1, echoing observations in humans and mice, and suggesting that a conserved set of maternal factors regulate chromatin remodeling prior to EGA. Subsequently, open chromatin established during EGA was primarily enriched for homeobox motifs, including that of DUX, a potential pioneer factor in mice and humans. Remarkably, the open chromatin landscape during bovine EGA clearly resembled that in humans, revealing that cattle could be a more relevant model for human development than mouse.