Chromatin jets define the properties of cohesin-driven in vivo loop extrusion
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Published version
OA Location
Author(s)
Type
Journal Article
Abstract
Complex genomes show intricate organization in three-dimensional (3D) nuclear space. Current models posit that cohesin extrudes loops to form self-interacting domains delimited by the DNA binding protein CTCF. Here, we describe and quantitatively characterize cohesin-propelled, jet-like chromatin contacts as landmarks of loop extrusion in quiescent mammalian lymphocytes. Experimental observations and polymer simulations indicate that narrow origins of loop extrusion favor jet formation. Unless constrained by CTCF, jets propagate symmetrically for 1-2 Mb, providing an estimate for the range of in vivo loop extrusion. Asymmetric CTCF binding deflects the angle of jet propagation as experimental evidence that cohesin-mediated loop extrusion can switch from bi- to unidirectional and is controlled independently in both directions. These data offer new insights into the physiological behavior of in vivo cohesin-mediated loop extrusion and further our understanding of the principles that underlie genome organization.
Date Issued
2022-09-30
Date Acceptance
2022-09-01
Citation
Molecular Cell, 2022, 82 (20), pp.3769-3780.e5
ISSN
1097-2765
Publisher
Cell Press
Start Page
3769
End Page
3780.e5
Journal / Book Title
Molecular Cell
Volume
82
Issue
20
Copyright Statement
© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
License URL
Sponsor
Wellcome Trust
Medical Research Council (MRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36182691
PII: S1097-2765(22)00854-1
Grant Number
099276/Z/12/Z
PO4050659629
Subjects
3D genome folding
CTCF
cohesin
loop extrusion
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2022-09-30