Non-equilibrium chromosome looping via molecular slip-links

TL;DR

This paper introduces a non-equilibrium model for chromatin loop formation driven by diffusive slip-links, explaining experimental observations without requiring motor activity, and reveals collective behaviors like loop extrusion bias.

Contribution

The study presents a novel diffusive sliding model for chromatin looping that accounts for experimental biases without motor proteins and uncovers emergent collective behaviors.

Findings

Diffusive slip-links can explain CTCF-mediated loop bias.

Multiple slip-links exhibit a ratchet effect at loading sites.

Large loops can form through collective osmotic pressure.

Abstract

We propose a model for the formation of chromatin loops based on the diffusive sliding of a DNA-bound factor which can dimerise to form a molecular slip-link. Our slip-links mimic the behaviour of cohesin-like molecules, which, along with the CTCF protein, stabilize loops which organize the genome. By combining 3D Brownian dynamics simulations and 1D exactly solvable non-equilibrium models, we show that diffusive sliding is sufficient to account for the strong bias in favour of convergent CTCF-mediated chromosome loops observed experimentally. Importantly, our model does not require any underlying, and energetically costly, motor activity of cohesin. We also find that the diffusive motion of multiple slip-links along chromatin may be rectified by an intriguing ratchet effect that arises if slip-links bind to the chromatin at a preferred "loading site". This emergent collective behaviour is driven by a 1D osmotic pressure which is set up near the loading point, and favours the extrusion of loops which are much larger than the ones formed by single slip-links.