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Effect of chromatin flexibility on diffusive loop extrusion via molecular slip-links

C. A. Brackley, J. Johnson, D. MichielettoiD, D. Marenduzzo

Abstract

We use Brownian dynamics simulations to study the formation of chromatin loops through diffusive sliding of molecular slip links, mimicking the behaviour of cohesin-like 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 elasticity of the chromatin fibre strongly affects this dynamical process, and find that diffusive loop extrusion is more efficient on stiffer chromatin regions. Efficiency is also enhanced if cohesin loading sites are close to regions where CTCF is bound. In light of the heterogeneous physical properties of eukaryotic chromatin, we suggest that our results should be relevant to the looping and organisation of interphase chromosomes in vivo.

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C. A. Brackley, J. Johnson, D. Michieletto+4 more·bioRxiv·Dec 21, 2016