RT Journal Article
SR Electronic
T1 Non-equilibrium chromosome looping via molecular slip-links
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 095992
DO 10.1101/095992
A1 C. A. Brackley
A1 J. Johnson
A1 D. Michieletto
A1 A. N. Morozov
A1 M. Nicodemi
A1 P. R. Cook
A1 D. Marenduzzo
YR 2016
UL http://biorxiv.org/content/early/2016/12/21/095992.abstract
AB 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.