Transcription-induced supercoiling as the driving force of chromatin loop extrusion during formation of TADs in interphase chromosomes.

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Version: Final published version
Serval ID
serval:BIB_DFCB79821A40
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transcription-induced supercoiling as the driving force of chromatin loop extrusion during formation of TADs in interphase chromosomes.
Journal
Nucleic acids research
Author(s)
Racko D., Benedetti F., Dorier J., Stasiak A.
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Publication state
Published
Issued date
28/02/2018
Peer-reviewed
Oui
Volume
46
Number
4
Pages
1648-1660
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Using molecular dynamics simulations, we show here that growing plectonemes resulting from transcription-induced supercoiling have the ability to actively push cohesin rings along chromatin fibres. The pushing direction is such that within each topologically associating domain (TAD) cohesin rings forming handcuffs move from the source of supercoiling, constituted by RNA polymerase with associated DNA topoisomerase TOP1, towards borders of TADs, where supercoiling is released by topoisomerase TOPIIB. Cohesin handcuffs are pushed by continuous flux of supercoiling that is generated by transcription and is then progressively released by action of TOPIIB located at TADs borders. Our model explains what can be the driving force of chromatin loop extrusion and how it can be ensured that loops grow quickly and in a good direction. In addition, the supercoiling-driven loop extrusion mechanism is consistent with earlier explanations proposing why TADs flanked by convergent CTCF binding sites form more stable chromatin loops than TADs flanked by divergent CTCF binding sites. We discuss the role of supercoiling in stimulating enhancer promoter contacts and propose that transcription of eRNA sends the first wave of supercoiling that can activate mRNA transcription in a given TAD.
Keywords
Cell Cycle Proteins/metabolism, Chromatin/chemistry, Chromosomal Proteins, Non-Histone/metabolism, Chromosomes/chemistry, DNA, Superhelical/chemistry, Interphase/genetics, Models, Genetic, Molecular Dynamics Simulation, Rotation, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
16/11/2017 19:02
Last modification date
20/08/2019 16:04
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