| Literature DB >> 31693890 |
Yi Zeng1, Rongfang Qiu1, Yang Yang1, Tianyang Gao1, Yu Zheng1, Wei Huang1, Jie Gao1, Kai Zhang1, Ruiqiong Liu1, Shuang Wang1, Yongqiang Hou1, Wenqian Yu1, Shuai Leng1, Dandan Feng1, Wei Liu1, Xi Zhang2, Yan Wang3.
Abstract
The histone methyl transferase enhancer of zeste homolog 2 (EZH2) is a master transcriptional regulator involved in histone H3 lysine 27 trimethylation. We aimed to elucidate the precise post-translational regulations of EZH2 and their role in cancer pathogenesis. Here, we show that SET and MYND domain containing 2 (SMYD2) directly methylates EZH2 at lysine 307 (K307) and enhances its stability, which can be relieved by the histone H3K4 demethylase lysine-specific demethylase 1 (LSD1). SMYD2 is critical for EZH2 function in repressing a cohort of genes governing several cancer-associated pathways. In addition, SMYD2 promotes breast cancer cell proliferation, epithelial-mesenchymal transition, and invasion through EZH2 K307 methylation, and it is markedly upregulated in various human cancers. Our data suggest that dynamic crosstalk between SMYD2-mediated EZH2 methylation plays an important role in fine-tuning EZH2 functions in chromatin recruitment and transcriptional repression.Entities:
Keywords: EZH2; SMYD2; breast cancer; methylation; post-translational modification; tumorigenesis
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Year: 2019 PMID： 31693890 DOI： 10.1016/j.celrep.2019.10.004
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423