Chromosome compaction and chromatin stiffness enhance diffusive loop extrusion by slip-link proteins

A. Bonato, C. A. Brackley, J. Johnson, D. Michieletto, D. Marenduzzo

Research output: Contribution to journalArticle

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 confined and collapsed chromatin conformations but that this enhancement is counteracted by the increased 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.

Original languageEnglish
Pages (from-to)2406-2414
Number of pages9
JournalSoft Matter
Volume16
Issue number9
Early online date13 Feb 2020
DOIs
Publication statusPublished - 4 Mar 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Condensed Matter Physics

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