Chromatin Accessibility Landscape in Human Early Embryos and Its Association with Evolution

The dynamics of the chromatin regulatory landscape during human early embryogenesis remains unknown. Using DNase I hypersensitive site (DHS) sequencing, we report that the chromatin accessibility landscape is gradually established during human early embryogenesis. Interestingly, the DHSs with OCT4 binding motifs are enriched at the timing of zygotic genome activation (ZGA) in humans, but not in mice. Consistently, OCT4 contributes to ZGA in humans, but not in mice. We further find that lower CpG promoters usually establish DHSs at later stages. Similarly, younger genes tend to establish promoter DHSs and are expressed at later embryonic stages, while older genes exhibit these features at earlier stages. Moreover, our data show that human active transposons SVA and HERV-K harbor DHSs and are highly expressed in early embryos, but not in differentiated tissues. In summary, our data provide an evolutionary developmental view for understanding the regulation of gene and transposon expression. [Display omitted] •The DHS landscape is gradually established during human embryo development•OCT4 contributes to zygotic genome activation in humans, but not in mice•Younger genes establish DHS at later stages, and older genes show the opposite trend•Human transposons SVA/HERVK harbor DHSs and are specifically expressed in embryos The dynamic landscape of open chromatin during early human embryogenesis provides a rich resource and insights into a zygotic genome activation.