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Key role for CTCF in establishing chromatin structure in human embryos

Author

Listed:
  • 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
    University of 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
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Zi-Jiang Chen

    (Shandong University, The Key laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University
    Shanghai Jiao Tong University
    Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics)

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.

Suggested Citation

  • Xuepeng Chen & Yuwen Ke & Keliang Wu & Han Zhao & Yaoyu Sun & Lei Gao & Zhenbo Liu & Jingye Zhang & Wenrong Tao & Zhenzhen Hou & Hui Liu & Jiang Liu & Zi-Jiang Chen, 2019. "Key role for CTCF in establishing chromatin structure in human embryos," Nature, Nature, vol. 576(7786), pages 306-310, December.
    • Handle: RePEc:nat:nature:v:576:y:2019:i:7786:d:10.1038_s41586-019-1812-0
    DOI: 10.1038/s41586-019-1812-0
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    Cited by:

    1. Markus Götz & Olivier Messina & Sergio Espinola & Jean-Bernard Fiche & Marcelo Nollmann, 2022. "Multiple parameters shape the 3D chromatin structure of single nuclei at the doc locus in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Mayank N. K. Choudhary & Kara Quaid & Xiaoyun Xing & Heather Schmidt & Ting Wang, 2023. "Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Hua Yu & Zhen Sun & Tianyu Tan & Hongru Pan & Jing Zhao & Ling Zhang & Jiayu Chen & Anhua Lei & Yuqing Zhu & Lang Chen & Yuyan Xu & Yaxin Liu & Ming Chen & Jinghao Sheng & Zhengping Xu & Pengxu Qian &, 2021. "rRNA biogenesis regulates mouse 2C-like state by 3D structure reorganization of peri-nucleolar heterochromatin," Nature Communications, Nature, vol. 12(1), pages 1-21, December.

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