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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Nils Krietenstein, Sameer Abraham, Sergey V Venev, Nezar Abdennur, Johan Gibcus, Tsung-Han S Hsieh, Krishna Mohan Parsi, Liyan Yang, René Maehr, Leonid A Mirny, Job Dekker, Oliver J Rando. Ultrastructural Details of Mammalian Chromosome Architecture. Molecular cell. 2020 May 07;78(3):554-565.e7

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PMID: 32213324

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