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MeCP2是一种微卫星结合蛋白
作者:小柯机器人 发布时间:2021/6/27 20:48:20

法国遗传与分子细胞生物学研究所Ali Hamiche等研究人员合作发现,MeCP2是一种微卫星结合蛋白,可保护CA重复序列免受核小体侵犯。该项研究成果发表在2021年6月25日出版的《科学》上。

研究人员发现,小鼠MeCP2是一种微卫星结合蛋白,可以特异性识别羟甲基化CA重复序列。MeCP2的耗竭改变了CA重复序列和核纤层相关域的染色质组织,并导致CA重复序列上的核小体积累和全基因组转录失调。与羟甲基化CA重复序列结合的MeCP2结构显示出特征性的DNA形状,且在5-羟甲基胞嘧啶(5hmC)处的几何结构明显改变,并被Arg133所特异性识别,其突变会导致Rett综合征。

这项工作将MeCP2鉴定为微卫星DNA结合蛋白,其靶向5hmC修饰的CA富含链并保持基因组区域无核小体,这提示了MeCP2功能障碍在Rett综合征中的作用。

据介绍,Rett综合征蛋白MeCP2被描述为甲基-CpG 结合蛋白,但其确切功能仍然未知。

附:英文原文

Title: MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion

Author: Abdulkhaleg Ibrahim, Christophe Papin, Kareem Mohideen-Abdul, Stéphanie Le Gras, Isabelle Stoll, Christian Bronner, Stefan Dimitrov, Bruno P. Klaholz, Ali Hamiche

Issue&Volume: 2021/06/25

Abstract: The Rett syndrome protein MeCP2 was described as a methyl-CpG-binding protein, but its exact function remains unknown. Here we show that mouse MeCP2 is a microsatellite binding protein that specifically recognizes hydroxymethylated CA repeats. Depletion of MeCP2 alters chromatin organization of CA repeats and lamina-associated domains and results in nucleosome accumulation on CA repeats and genome-wide transcriptional dysregulation. The structure of MeCP2 in complex with a hydroxymethylated CA repeat reveals a characteristic DNA shape, with considerably modified geometry at the 5-hydroxymethylcytosine, which is recognized specifically by Arg133, a key residue whose mutation causes Rett syndrome. Our work identifies MeCP2 as a microsatellite DNA binding protein that targets the 5hmC-modified CA-rich strand and maintains genome regions nucleosome-free, suggesting a role for MeCP2 dysfunction in Rett syndrome.

DOI: 10.1126/science.abd5581

Source: https://science.sciencemag.org/content/372/6549/eabd5581

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037