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

Author:

Tang Xiuxiao,Zeng Pengguihang,Liu Kezhi,Qing Li,Sun Yifei,Liu Xinyi,Lu Lizi,Wei Chao,Wang Jia,Jiang Shaoshuai,Sun Jun,Chang Wakam,Yu Haopeng,Chen HebingORCID,Zhou Jiaguo,Xu Chengfang,Fan LiliORCID,Miao Yi-LiangORCID,Ding JunjunORCID

Abstract

AbstractCCCTC-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.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

Publisher

Springer Science and Business Media LLC

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