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

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

  • Nat Commun. 2024 Apr 1;15(1):2813. doi: 10.1038/s41467-024-47048-3.
Xiuxiao Tang # 1 2 3 4 5,  Pengguihang Zeng # 1 2 3 4,  Kezhi Liu 1 2 3 4,  Li Qing 1 2 3 4,  Yifei Sun 1 2 3 4,  Xinyi Liu 1 2 3 4,  Lizi Lu 1 2 3 4,  Chao Wei 1 2 3 4,  Jia Wang 6,  Shaoshuai Jiang 1 2 3 4,  Jun Sun 7 8,  Wakam Chang 9,  Haopeng Yu 7 8,  Hebing Chen 10,  Jiaguo Zhou 5,  Chengfang Xu 11,  Lili Fan 12,  Yi-Liang Miao 13,  Junjun Ding 14 15 16 17 18
Affiliations

Affiliations

  • 1 RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
  • 2 Department of Rehabilitation Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518107, China.
  • 3 Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
  • 4 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China.
  • 5 Department of Pharmacology and Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
  • 6 GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • 7 West China Biomedical Big Data Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, 610041, China.
  • 8 Med-X Center for Informatics, Sichuan University, Chengdu, 610041, China.
  • 9 Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
  • 10 Institute of Health Service and Transfusion Medicine, Beijing, 100850, China.
  • 11 The obstetric and gynecology Department of The third affiliated hospital of Sun Yat-Sen University, Guangzhou, China. [email protected].
  • 12 Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, China. [email protected].
  • 13 Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China. [email protected].
  • 14 RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China. [email protected].
  • 15 Department of Rehabilitation Medicine, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518107, China. [email protected].
  • 16 Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China. [email protected].
  • 17 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China. [email protected].
  • 18 West China Biomedical Big Data Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, 610041, China. [email protected].
  • # Contributed equally.
PMID: 38561336 DOI: 10.1038/s41467-024-47048-3
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.

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