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

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, Chengfang Xu (), Lili Fan (), Yi-Liang Miao () and Junjun Ding ()
Additional contact information
Xiuxiao Tang: Sun Yat-Sen University
Pengguihang Zeng: Sun Yat-Sen University
Kezhi Liu: Sun Yat-Sen University
Li Qing: Sun Yat-Sen University
Yifei Sun: Sun Yat-Sen University
Xinyi Liu: Sun Yat-Sen University
Lizi Lu: Sun Yat-Sen University
Chao Wei: Sun Yat-Sen University
Jia Wang: Guangzhou Medical University
Shaoshuai Jiang: Sun Yat-Sen University
Jun Sun: Sichuan University
Wakam Chang: University of Macau
Haopeng Yu: 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

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47048-3

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