组蛋白赖氨酸甲基转移酶与核小体的结合：结构基础、调控机制及治疗意义。

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.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB), Meilong Road 130, Shanghai 200237, China.

Protein Cell. 2023 Apr 13;14(3):165-179. doi: 10.1093/procel/pwac032.

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.

组蛋白赖氨酸甲基转移酶（HKMTs）将甲基基团添加到组蛋白赖氨酸残基上，在调节染色质结构和基因表达方面发挥着重要作用。在过去的几十年中，HKMTs 的结构和功能得到了广泛的研究，极大地促进了我们对组蛋白甲基化动态调控的理解。在这里，我们综述了近年来与核小体（H3K4、H3K27、H3K36、H3K79 和 H4K20 甲基转移酶）复合物中代表性 HKMTs 的结构研究进展，重点介绍了这些 HKMTs 识别核小体和跨组蛋白串扰的分子机制。这些结构研究阐明了 HKMTs 在肿瘤发生中的作用，并为开发针对癌症中 HKMTs 的新治疗方法提供了基础。