Ultrastructural Details of Mammalian Chromosome Architecture
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Molecular Cell |
Volume | 78 |
Issue number | 3 |
Pages (from-to) | 554-565.e7 |
ISSN | 1097-2765 |
DOIs | |
Publication status | Published - 7 May 2020 |
Externally published | Yes |
Bibliographical note
Copyright © 2020 Elsevier Inc. All rights reserved.
- Animals, CCCTC-Binding Factor/metabolism, Cells, Cultured, Chromatin/chemistry, Chromosomes, Human/ultrastructure, Chromosomes, Mammalian/ultrastructure, Embryonic Stem Cells/cytology, Fibroblasts/cytology, Humans, Male, Mammals/genetics, Nucleosomes/metabolism, Signal-To-Noise Ratio
Research areas
ID: 301925297