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

Cell. 2018 Mar 22;173(1):248-259.e15. doi: 10.1016/j.cell.2018.02.028. Epub 2018 Mar 8.


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.

Keywords: DHS; chromatin accessibility; evolution; gene age; human embryos; transposon; zygotic genome activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Chromatin / metabolism*
  • CpG Islands
  • DNA Methylation
  • DNA Transposable Elements / genetics
  • Deoxyribonuclease I / metabolism
  • Down-Regulation
  • Embryo, Mammalian / metabolism*
  • Embryonic Development
  • Evolution, Molecular*
  • Humans
  • Mice
  • Octamer Transcription Factor-3 / antagonists & inhibitors
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Zygote / metabolism


  • Chromatin
  • DNA Transposable Elements
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Small Interfering
  • Deoxyribonuclease I