The structural basis for cohesin-CTCF-anchored loops
The structural basis for cohesin-CTCF-anchored loops
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DOI：
10.1038/s41586-019-1910-z
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发表时间：
2020-01-06
期刊：
影响因子：
64.8
通讯作者：
Panne, Daniel
中科院分区：
文献类型：
--
作者：
Li, Yan;Haarhuis, Judith H. I.;Panne, Daniel
粘附素催化基因组折叠成由CTCF1锚定的环。粘附素和CTCF如何构建3D基因组的分子机制尚不清楚。在这里，我们显示了CTCFN末端的一个片段与人粘附素的SA2-SCC1亚基相互作用。我们报道了SA2-SCC1与CTCF形成的络合物的晶体结构，其分辨率为2.7埃，揭示了相互作用的分子基础。我们证明了这种相互作用是CTCF锚定环所特需的，并有助于粘附素在CTCF结合位点的定位。在一些已建立的和新发现的粘附素配体中也存在类似的基序，包括粘附素释放因子WAPL(2，3)。我们的数据表明，CTCF通过保护粘附素不受环释放的影响，使染色质环得以形成。这些结果为揭示粘附素和CTCF动态调节染色质折叠的分子机制提供了基础。人粘附素与CTCF络合物中SA2-SCC1亚基的晶体结构揭示了粘附素-CTCF相互作用的分子基础，使染色质折叠能够动态调节。
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 human cohesin. We report a crystal structure of SA2-SCC1 in complex with CTCF at a resolution of 2.7 angstrom, which 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 newly identified cohesin ligands, including the cohesin release factor WAPL(2,3). Our data suggest that CTCF enables the formation of chromatin loops by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables the dynamic regulation of chromatin folding by cohesin and CTCF.The crystal structure of the SA2-SCC1 subunits of human cohesin in complex with CTCF reveals the molecular basis of the cohesin-CTCF interaction that enables the dynamic regulation of chromatin folding.