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Chromosome Compaction and Chromatin Stiffness Enhance Diffusive Loop Extrusion by Slip-Link Proteins

Abstract

We use Brownian dynamics simulations to study the formation of chromatin loops through diffusive sliding of slip-link-like proteins, mimicking the behaviour of cohesin molecules. We recently proposed that diffusive sliding is sufficient to explain the extrusion of chromatin loops of hundreds of kilo-base-pairs (kbp), which may then be stabilised by interactions between cohesin and CTCF proteins. Here we show that the flexibility of the chromatin fibre strongly affects this dynamical process, and find that diffusive loop extrusion is more efficient on stiffer chromatin regions. We also show that the dynamics of loop formation are faster in collapsed chromatin conformations but that this enhancement is counteracted by the increasing crowding. We provide a simple theoretical argument explaining why stiffness and collapsed conformations favour diffusive extrusion. In light of the heterogeneous physical and conformational properties of eukaryotic chromatin, we suggest that our results are relevant to understand the looping and organisation of interphase chromosomes in vivo.

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Article information


Submitted
16 Sep 2019
Accepted
11 Feb 2020
First published
13 Feb 2020

Soft Matter, 2020, Accepted Manuscript
Article type
Paper

Chromosome Compaction and Chromatin Stiffness Enhance Diffusive Loop Extrusion by Slip-Link Proteins

A. Bonato, C. A. Brackley, J. Johnson, D. Michieletto and D. Mareduzzo, Soft Matter, 2020, Accepted Manuscript , DOI: 10.1039/C9SM01875A

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