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Ultrastructural Details of Mammalian Chromosome Architecture.
Molecular Cell ( IF 14.5 ) Pub Date : 2020-03-25 , DOI: 10.1016/j.molcel.2020.03.003
Nils Krietenstein 1 , Sameer Abraham 2 , Sergey V Venev 3 , Nezar Abdennur 2 , Johan Gibcus 3 , Tsung-Han S Hsieh 4 , Krishna Mohan Parsi 5 , Liyan Yang 3 , René Maehr 5 , Leonid A Mirny 2 , Job Dekker 6 , Oliver J Rando 1
Affiliation  

Over the past decade, 3C-related methods have provided remarkable insights into chromosome folding in vivo. To overcome the limited resolution of prior studies, we extend a recently developed Hi-C variant, Micro-C, to map chromosome architecture at nucleosome resolution in human ESCs and fibroblasts. Micro-C robustly captures known features of chromosome folding including compartment organization, topologically associating domains, and interactions between CTCF binding sites. In addition, Micro-C provides a detailed map of nucleosome positions and localizes contact domain boundaries with nucleosomal precision. Compared to Hi-C, Micro-C exhibits an order of magnitude greater dynamic range, allowing the identification of ∼20,000 additional loops in each cell type. Many newly identified peaks are localized along extrusion stripes and form transitive grids, consistent with their anchors being pause sites impeding cohesin-dependent loop extrusion. Our analyses comprise the highest-resolution maps of chromosome folding in human cells to date, providing a valuable resource for studies of chromosome organization.

中文翻译:

哺乳动物染色体结构的超微结构细节。

在过去的十年中,与3C相关的方法为体内染色体折叠提供了非凡的见解。为了克服先前研究的有限分辨率,我们扩展了最近开发的Hi-C变体Micro-C,以人类核干细胞和成纤维细胞中核小体分辨率的染色体结构图谱。Micro-C强大地捕获了染色体折叠的已知特征,包括区室组织,拓扑关联域以及CTCF结合位点之间的相互作用。另外,Micro-C提供了核小体位置的详细图,并以核小体精度定位了接触域边界。与Hi-C相比,Micro-C的动态范围更大,可在每种细胞类型中识别出约20,000个额外的环。许多新发现的峰沿挤出条纹定位并形成传递网格,与它们的锚点是阻碍粘着蛋白依赖性环挤出的停滞位点一致。我们的分析包括迄今为止人类细胞中最高分辨率的染色体折叠图,为染色体组织的研究提供了宝贵的资源。
更新日期:2020-03-25
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