Ultrastructural Details of Mammalian Chromosome Architecture
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Ultrastructural Details of Mammalian Chromosome Architecture. / Krietenstein, Nils; Abraham, Sameer; Venev, Sergey V; Abdennur, Nezar; Gibcus, Johan; Hsieh, Tsung-Han S; Parsi, Krishna Mohan; Yang, Liyan; Maehr, René; Mirny, Leonid A; Dekker, Job; Rando, Oliver J.
In: Molecular Cell, Vol. 78, No. 3, 07.05.2020, p. 554-565.e7.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Ultrastructural Details of Mammalian Chromosome Architecture
AU - Krietenstein, Nils
AU - Abraham, Sameer
AU - Venev, Sergey V
AU - Abdennur, Nezar
AU - Gibcus, Johan
AU - Hsieh, Tsung-Han S
AU - Parsi, Krishna Mohan
AU - Yang, Liyan
AU - Maehr, René
AU - Mirny, Leonid A
AU - Dekker, Job
AU - Rando, Oliver J
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2020/5/7
Y1 - 2020/5/7
N2 - 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.
AB - 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.
KW - Animals
KW - CCCTC-Binding Factor/metabolism
KW - Cells, Cultured
KW - Chromatin/chemistry
KW - Chromosomes, Human/ultrastructure
KW - Chromosomes, Mammalian/ultrastructure
KW - Embryonic Stem Cells/cytology
KW - Fibroblasts/cytology
KW - Humans
KW - Male
KW - Mammals/genetics
KW - Nucleosomes/metabolism
KW - Signal-To-Noise Ratio
U2 - 10.1016/j.molcel.2020.03.003
DO - 10.1016/j.molcel.2020.03.003
M3 - Journal article
C2 - 32213324
VL - 78
SP - 554-565.e7
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 3
ER -
ID: 301925297