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核小体结合的DNA甲基转移酶DNMT3A和DNMT3B结构获解析
2020-09-24 11:24

中科院上海药物研究所徐华强等研究人员合作揭示核小体结合的DNA甲基转移酶DNMT3A和DNMT3B结构。相关论文于2020年9月23日在线发表在《自然》杂志上。

研究人员报道了具有催化能力的DNMT3A2、无催化活性的辅助亚基DNMT3B3和侧翼为连接子DNA的核小体核心颗粒的三元复合物冷冻电镜结构。辅助DNMT3B3的催化样结构域与核小体核心的酸性斑块结合,这指导了DNMT3A2与接头DNA的结合。这种排布的空间限制表明,核糖体DNA必须相对于核小体核心移动才能发生从头甲基化。
 
据介绍,从头DNA甲基转移酶3A和3B介导的CpG甲基化对于哺乳动物的发育和分化至关重要,并且在癌症中常常失调。这两个DNMT优先结合核小体,但不能使包裹在核小体核心2上的DNA甲基化,并且它们支持位于定位的核小体的接头DNA的甲基化。 
 
附:英文原文

Title: Structure of nucleosome-bound DNA methyltransferases DNMT3A and DNMT3B

Author: Ting-Hai Xu, Minmin Liu, X. Edward Zhou, Gangning Liang, Gongpu Zhao, H. Eric Xu, Karsten Melcher, Peter A. Jones

Issue&Volume: 2020-09-23

Abstract: CpG methylation by de novo DNA methyltransferases (DNMTs) 3A and 3B is essential for mammalian development and differentiation and is frequently dysregulated in cancer1. These two DNMTs preferentially bind to nucleosomes, yet cannot methylate the DNA wrapped around the nucleosome core2, and they favour the methylation of linker DNA at positioned nucleosomes3,4. Here we present the cryo-electron microscopy structure of a ternary complex of catalytically competent DNMT3A2, the catalytically inactive accessory subunit DNMT3B3 and a nucleosome core particle flanked by linker DNA. The catalytic-like domain of the accessory DNMT3B3 binds to the acidic patch of the nucleosome core, which orients the binding of DNMT3A2 to the linker DNA. The steric constraints of this arrangement suggest that nucleosomal DNA must be moved relative to the nucleosome core for de novo methylation to occur.

DOI: 10.1038/s41586-020-2747-1

Source: https://www.nature.com/articles/s41586-020-2747-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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