Chromatin analysis in human early development reveals epigenetic transition during ZGA

Jingyi Wu, Jiawei Xu, Bofeng Liu, Guidong Yao, Peizhe Wang, Zili Lin, Bo Huang, Xuepeng Wang, Tong Li, Senlin Shi, Nan Zhang, Fuyu Duan, Jia Ming, Xiangyang Zhang, Wenbin Niu, Wenyan Song, Haixia Jin, Yihong Guo, Shanjun Dai, Linli Hu, Lanlan Fang, Qiujun Wang, Yuanyuan Li, Wei Li, Jie Na (), Wei Xie () and Yingpu Sun ()
Additional contact information
Jingyi Wu: Tsinghua University
Jiawei Xu: The First Affiliated Hospital of Zhengzhou University
Bofeng Liu: Tsinghua University
Guidong Yao: The First Affiliated Hospital of Zhengzhou University
Peizhe Wang: Tsinghua University
Zili Lin: Tsinghua University
Bo Huang: Peking University
Xuepeng Wang: Chinese Academy of Sciences
Tong Li: The First Affiliated Hospital of Zhengzhou University
Senlin Shi: The First Affiliated Hospital of Zhengzhou University
Nan Zhang: The First Affiliated Hospital of Zhengzhou University
Fuyu Duan: Tsinghua University
Jia Ming: Tsinghua University
Xiangyang Zhang: The First Affiliated Hospital of Zhengzhou University
Wenbin Niu: The First Affiliated Hospital of Zhengzhou University
Wenyan Song: The First Affiliated Hospital of Zhengzhou University
Haixia Jin: The First Affiliated Hospital of Zhengzhou University
Yihong Guo: The First Affiliated Hospital of Zhengzhou University
Shanjun Dai: The First Affiliated Hospital of Zhengzhou University
Linli Hu: The First Affiliated Hospital of Zhengzhou University
Lanlan Fang: The First Affiliated Hospital of Zhengzhou University
Qiujun Wang: Tsinghua University
Yuanyuan Li: Tsinghua University
Wei Li: Chinese Academy of Sciences
Jie Na: Tsinghua University
Wei Xie: Tsinghua University
Yingpu Sun: The First Affiliated Hospital of Zhengzhou University

Nature, 2018, vol. 557, issue 7704, 256-260

Abstract: Abstract Upon fertilization, drastic chromatin reorganization occurs during preimplantation development 1 . However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored in humans. Here we investigate chromatin states in human preimplantation development using an improved assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) 2 . We find widespread accessible chromatin regions in early human embryos that overlap extensively with putative cis-regulatory sequences and transposable elements. Integrative analyses show both conservation and divergence in regulatory circuitry between human and mouse early development, and between human pluripotency in vivo and human embryonic stem cells. In addition, we find widespread open chromatin regions before zygotic genome activation (ZGA). The accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others reside in distal regions that overlap with DNA hypomethylated domains in human oocytes and are enriched for transcription factor-binding sites. A large portion of these regions then become inaccessible after ZGA in a transcription-dependent manner. Notably, such extensive chromatin reorganization during ZGA is conserved in mice and correlates with the reprogramming of the non-canonical histone mark H3K4me3, which is uniquely linked to genome silencing3–5. Taken together, these data not only reveal a conserved principle that underlies the chromatin transition during mammalian ZGA, but also help to advance our understanding of epigenetic reprogramming during human early development and in vitro fertilization.

Date: 2018
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DOI: 10.1038/s41586-018-0080-8

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