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cohesin-CTCF锚定DNA环的结构基础获解析
2020-01-07 11:08

法国欧洲分子生物实验室Daniel Panne、Kyle W. Muir与荷兰癌症研究所Benjamin D. Rowland、Elzo de Wit等研究人员合作解析了黏连蛋白(cohesin)与CTCF锚定DNA环的结构基础。2020年1月6日,国际知名学术期刊《自然》在线发表了这一成果。

研究人员发现,CTCF N末端的一段与cohesin的SA2-SCC1亚基相互作用。SA2-SCC1与CTCF结合后的2.6Å晶体结构揭示了相互作用的分子基础。研究人员证明了这种相互作用是CTCF锚定环特有的,并且有助于在CTCF结合位点定位cohesin。类似的基序存在于许多已建立的新型cohesin配体中,包括cohesin释放因子WAPL。

这些数据表明,CTCF通过保护cohesin免受环释放而使染色质环形成。这些结果提供了对相关分子机理的基础见解,即通过cohesin和CTCF实现对染色质折叠的动态调节。

据悉,cohesin催化基因组折叠成由CTCF锚定的环。cohesin和CTCF如何构成3D基因组的分子机制仍不清楚。

附:英文原文

Title: The structural basis for cohesin–CTCF-anchored loops

Author: Yan Li, Judith H. I. Haarhuis, ngela Sedeo Cacciatore, Roel Oldenkamp, Marjon S. van Ruiten, Laureen Willems, Hans Teunissen, Kyle W. Muir, Elzo de Wit, Benjamin D. Rowland, Daniel Panne

Issue&Volume: 2020-01-06

Abstract: Cohesin catalyses the folding of the genome into loops that are anchored by CTCF1. The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2-SCC1 subunits of cohesin. A 2.6 crystal structure of SA2-SCC1 in complex with CTCF reveals the molecular basis of the interaction. We demonstrate that this interaction is specifically required for CTCF-anchored loops and contributes to the positioning of cohesin at CTCF-binding sites. A similar motif is present in a number of established and novel cohesin ligands, including the cohesin release factor WAPL2,3. Our data suggest that CTCF enables chromatin loop formation by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables dynamic regulation of chromatin folding by cohesin and CTCF.

DOI: 10.1038/s41586-019-1910-z

Source: https://www.nature.com/articles/s41586-019-1910-z

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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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