The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications.

Yanjing LI; Kexue GE; Tingting LI; Run Cai; Yong Chen

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The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications.

Author: Yanjing LI ¹ ; Kexue GE ¹ ; Tingting LI ¹ ; Run CAI ¹ ; Yong CHEN ¹
Author Information

1. State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: cryo-EM structures; epigenetics; histone methylation; histone methyltransferases; nucleosome; tumorigenesis
MeSH: Nucleosomes; Histones/metabolism*; Histone-Lysine N-Methyltransferase/metabolism*; Lysine/metabolism*; Methyltransferases/metabolism*; Methylation
From: Protein & Cell 2023;14(3):165-179
CountryChina
Language:English
Abstract: Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs' roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.