Menin reads H3K79me2 mark in a nucleosomal context

• 成果类型: Article
• 署名作者: Lin, Jianwei; Wu, Yiping; Tian, Gaofei; Yu, Daqi; Yang, Eunjeong; Lam, Wai Hei; Liu, Zheng; Jing, Yihang; Dang, Shangyu; Bao, Xiucong; Wong, Jason Wing Hon; Zhai, Yuanliang; Li, Xiang David
• 署名单位: University of Hong Kong; Hong Kong University of Science & Technology; Shenzhen Bay Laboratory; University of Hong Kong; University of Hong Kong
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13938
• DOI: 10.1126/science.adc9318
• 发表日期: 2023-02-17
• 页码: 717-723
• 关键词: histone modifications; tumor-suppressor; dot1l; mll; methylation; protein; inhibition; enhancers; differentiation; dimethylation

摘要

Methylation of histone H3 lysine-79 (H3K79) is an epigenetic mark for gene regulation in development, cellular differentiation, and disease progression. However, how this histone mark is translated into downstream effects remains poorly understood owing to a lack of knowledge about its readers. We developed a nucleosome-based photoaffinity probe to capture proteins that recognize H3K79 dimethylation (H3K79me2) in a nucleosomal context. In combination with a quantitative proteomics approach, this probe identified menin as a H3K79me2 reader. A cryo-electron microscopy structure of menin bound to an H3K79me2 nucleosome revealed that menin engages with the nucleosome using its fingers and palm domains and recognizes the methylation mark through a p-cation interaction. In cells, menin is selectively associated with H3K79me2 on chromatin, particularly in gene bodies.