RT Journal Article
SR Electronic
T1 MCM complexes are barriers that restrict cohesin-mediated loop extrusion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.15.340356
DO 10.1101/2020.10.15.340356
A1 Bart J. H. Dequeker
A1 Hugo B. Brandão
A1 Matthias J. Scherr
A1 Johanna Gassler
A1 Sean Powell
A1 Imre Gaspar
A1 Ilya M. Flyamer
A1 Wen Tang
A1 Roman Stocsits
A1 Iain F. Davidson
A1 Jan-Michael Peters
A1 Karl E. Duderstadt
A1 Leonid A. Mirny
A1 Kikuё Tachibana
YR 2020
UL http://biorxiv.org/content/early/2020/10/15/2020.10.15.340356.abstract
AB Eukaryotic genomes are compacted into loops and topologically associating domains (TADs), which contribute to transcription, recombination and genomic stability. Cohesin extrudes DNA into loops that are thought to lengthen until CTCF boundaries are encountered. Little is known about whether loop extrusion is impeded by DNA-bound macromolecular machines. We demonstrate that the replicative helicase MCM is a barrier that restricts loop extrusion in G1 phase. Single-nucleus Hi-C of one-cell embryos revealed that MCM loading reduces CTCF-anchored loops and decreases TAD boundary insulation, suggesting loop extrusion is impeded before reaching CTCF. Single-molecule imaging shows that MCMs are physical barriers that frequently constrain cohesin translocation in vitro. Simulations are consistent with MCMs as abundant, random barriers. We conclude that distinct loop extrusion barriers contribute to shaping 3D genomes.One Sentence Summary MCM complexes are obstacles that impede the formation of CTCF-anchored loops.Competing Interest StatementThe authors have declared no competing interest.