CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101 Beijing, China.
Center for Reproductive Medicine, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan, 250001 Shandong, China.
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.
人类早期胚胎发生过程中染色质调控景观的动态变化尚不清楚。使用 DNase I 超敏位点 (DHS) 测序，我们报告说，在人类早期胚胎发生过程中，染色质可及性景观逐渐建立。有趣的是，在人类中，具有 OCT4 结合基序的 DHSs 在合子基因组激活 (ZGA) 时富集，但在小鼠中没有。一致地，OCT4 有助于人类的 ZGA，但不是在小鼠中。我们进一步发现，低 CpG 启动子通常在后期建立 DHS。同样，较年轻的基因往往在后期胚胎阶段建立启动子 DHS 并表达，而较老的基因则在早期阶段表现出这些特征。此外，我们的数据表明，人类活跃的转座子 SVA 和 HERV-K 含有 DHS，并且在早期胚胎中高度表达，但在分化组织中不表达。总之，我们的数据为理解基因和转座子表达的调控提供了一个进化发育的视角。
