Extrusion without a motor: a new take on the loop extrusion model of genome organization

TL;DR

This paper proposes a motor-free model for chromatin loop extrusion driven by thermal motion, supported by theoretical and simulation evidence that such diffusion can produce biologically relevant loops.

Contribution

It introduces a novel hypothesis that thermal diffusion, without motor proteins, can drive chromatin loop extrusion, challenging the traditional motor-dependent models.

Findings

Diffusive extrusion can generate loops of observed sizes.

A ratchet effect enhances loop growth via osmotic pressure.

Simulations support feasibility of motor-free loop formation.

Abstract

Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion. Using theoretical modelling and computer simulations we ask whether such diffusive extrusion could feasibly generate loops. Our simulations uncover an interesting ratchet effect (where an osmotic pressure promotes loop growth), and suggest, by comparison to recent in vitro and in vivo measurements, that diffusive extrusion can in principle generate loops of the size observed in the data. Extra View on : C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, and D. Marenduzzo "Non-equilibrium chromosome looping via molecular slip-links", Physical Review Letters 119, 138101 (2017)