Key role for CTCF in establishing chromatin structure in human embryos

Xuepeng Chen, Yuwen Ke, Keliang Wu, Han Zhao, Yaoyu Sun, Lei Gao, Zhenbo Liu, Jingye Zhang, Wenrong Tao, Zhenzhen Hou, Hui Liu, Jiang Liu () and Zi-Jiang Chen ()
Additional contact information
Xuepeng Chen: Beijing Institute of Genomics, Chinese Academy of Sciences
Yuwen Ke: Beijing Institute of Genomics, Chinese Academy of Sciences
Keliang Wu: Shandong University, The Key laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University
Han Zhao: Shandong University, The Key laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University
Yaoyu Sun: Beijing Institute of Genomics, Chinese Academy of Sciences
Lei Gao: Beijing Institute of Genomics, Chinese Academy of Sciences
Zhenbo Liu: Beijing Institute of Genomics, Chinese Academy of Sciences
Jingye Zhang: Shandong University, The Key laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University
Wenrong Tao: Shandong University, The Key laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University
Zhenzhen Hou: Shandong University, The Key laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University
Hui Liu: Shandong University, The Key laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University
Jiang Liu: Beijing Institute of Genomics, Chinese Academy of Sciences
Zi-Jiang Chen: Shandong University, The Key laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University

Nature, 2019, vol. 576, issue 7786, 306-310

Abstract: Abstract In the interphase of the cell cycle, chromatin is arranged in a hierarchical structure within the nucleus1,2, which has an important role in regulating gene expression3–6. However, the dynamics of 3D chromatin structure during human embryogenesis remains unknown. Here we report that, unlike mouse sperm, human sperm cells do not express the chromatin regulator CTCF and their chromatin does not contain topologically associating domains (TADs). Following human fertilization, TAD structure is gradually established during embryonic development. In addition, A/B compartmentalization is lost in human embryos at the 2-cell stage and is re-established during embryogenesis. Notably, blocking zygotic genome activation (ZGA) can inhibit TAD establishment in human embryos but not in mouse or Drosophila. Of note, CTCF is expressed at very low levels before ZGA, and is then highly expressed at the ZGA stage when TADs are observed. TAD organization is significantly reduced in CTCF knockdown embryos, suggesting that TAD establishment during ZGA in human embryos requires CTCF expression. Our results indicate that CTCF has a key role in the establishment of 3D chromatin structure during human embryogenesis.

Date: 2019
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DOI: 10.1038/s41586-019-1812-0

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