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The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation

Author

Listed:
  • Xiuxiao Tang

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

  • Pengguihang Zeng

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

  • Kezhi Liu

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

  • Li Qing

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

  • Yifei Sun

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

  • Xinyi Liu

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

  • Lizi Lu

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

  • Chao Wei

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

  • Jia Wang

    (Guangzhou Medical University)

  • Shaoshuai Jiang

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

  • Jun Sun

    (Sichuan University
    Sichuan University)

  • Wakam Chang

    (University of Macau)

  • Haopeng Yu

    (Sichuan University
    Sichuan University)

  • Hebing Chen

    (Institute of Health Service and Transfusion Medicine)

  • Jiaguo Zhou

    (Sun Yat-Sen University)

  • Chengfang Xu

    (The obstetric and gynecology Department of The third affiliated hospital of Sun Yat-Sen University)

  • Lili Fan

    (Jinan University)

  • Yi-Liang Miao

    (Huazhong Agricultural University)

  • Junjun Ding

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

Abstract

CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood. In this study, we uncovered the PTM profiling of CTCF and demonstrated that CTCF can be O-GlcNAcylated and arginine methylated. Functionally, we demonstrated that O-GlcNAcylation inhibits CTCF binding to chromatin. Meanwhile, deficiency of CTCF O-GlcNAcylation results in the disruption of loop domains and the alteration of chromatin loops associated with cellular development. Furthermore, the deficiency of CTCF O-GlcNAcylation increases the expression of developmental genes and negatively regulates maintenance and establishment of stem cell pluripotency. In conclusion, these results provide key insights into the role of PTMs for the 3D chromatin structure.

Suggested Citation

  • Xiuxiao Tang & Pengguihang Zeng & Kezhi Liu & Li Qing & Yifei Sun & Xinyi Liu & Lizi Lu & Chao Wei & Jia Wang & Shaoshuai Jiang & Jun Sun & Wakam Chang & Haopeng Yu & Hebing Chen & Jiaguo Zhou & Cheng, 2024. "The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47048-3
    DOI: 10.1038/s41467-024-47048-3
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    References listed on IDEAS

    as
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