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

TL;DR

This study uses simulations to show that chromatin stiffness and compaction significantly enhance the efficiency of diffusive loop extrusion by slip-link proteins, providing insights into chromosome organization.

Contribution

It demonstrates how chromatin physical properties influence diffusive loop extrusion, highlighting the importance of stiffness and conformation in chromatin dynamics.

Findings

Stiffer chromatin regions facilitate more efficient diffusive loop extrusion.

Confined and collapsed chromatin conformations speed up loop formation.

Increased crowding counteracts the acceleration in loop formation.

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.