研究人员开发了一种基于核小体的光亲和探针，以捕获在核小体环境中识别组蛋白H3第79位赖氨酸二甲基化（H3K79me2）的蛋白质。通过结合定量蛋白质组学方法，该探针将menin鉴定为H3K79me2阅读器。在冷冻电镜下，menin与一个H3K79me2核小体结合，其与位于手指和手掌结构域的核小体结合，并通过π-阳离子相互作用识别甲基化标记。在细胞中，menin与染色质上的H3K79me2选择性结合，尤其是在基因体中。
据了解，组蛋白H3K79的甲基化是发育、细胞分化和疾病进展中基因调控的表观遗传标记。然而，由于缺乏对其阅读器的了解，该组蛋白标记如何转化为下游效应仍然知之甚少。
附：英文原文
Title: Menin “reads” H3K79me2 mark in a nucleosomal context
Author: Jianwei Lin, Yiping Wu, Gaofei Tian, Daqi Yu, Eunjeong Yang, Wai Hei Lam, Zheng Liu, Yihang Jing, Shangyu Dang, Xiucong Bao, Jason Wing Hon Wong, Yuanliang Zhai, Xiang David Li
Issue&Volume: 2023-02-17
Abstract: 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 π-cation interaction. In cells, menin is selectively associated with H3K79me2 on chromatin, particularly in gene bodies.
DOI: adc9318
Source: https://www.science.org/doi/10.1126/science.adc9318