Nonequilibrium chromosome looping via molecular slip links

We propose a model for the formation of chromatin loops based on the diffusive sliding of molecular slip links. These mimic the behavior of molecules like cohesin, which, along with the CTCF protein, stabilize loops which contribute to organizing the genome. By combining 3D Brownian dynamics simulat...

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Main Authors: Brackley, C, Johnson, J, Michieletto, D, Morozov, A, Nicodemi, M, Cook, P, Marenduzzo, D
Format: Journal article
Published: American Physical Society 2017
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author Brackley, C
Johnson, J
Michieletto, D
Morozov, A
Nicodemi, M
Cook, P
Marenduzzo, D
author_facet Brackley, C
Johnson, J
Michieletto, D
Morozov, A
Nicodemi, M
Cook, P
Marenduzzo, D
author_sort Brackley, C
collection OXFORD
description We propose a model for the formation of chromatin loops based on the diffusive sliding of molecular slip links. These mimic the behavior of molecules like cohesin, which, along with the CTCF protein, stabilize loops which contribute to organizing the genome. By combining 3D Brownian dynamics simulations and 1D exactly solvable nonequilibrium models, we show that diffusive sliding is sufficient to account for the strong bias in favor of convergent CTCF-mediated chromosome loops observed experimentally. We also find that the diffusive motion of multiple slip links along chromatin is rectified by an intriguing ratchet effect that arises if slip links bind to the chromatin at a preferred “loading site.” This emergent collective behavior favors the extrusion of loops which are much larger than the ones formed by single slip links.
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spelling oxford-uuid:5b9a205a-1e6f-41e1-93c8-9e781709863d2022-03-26T17:23:05ZNonequilibrium chromosome looping via molecular slip linksJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5b9a205a-1e6f-41e1-93c8-9e781709863dSymplectic Elements at OxfordAmerican Physical Society2017Brackley, CJohnson, JMichieletto, DMorozov, ANicodemi, MCook, PMarenduzzo, DWe propose a model for the formation of chromatin loops based on the diffusive sliding of molecular slip links. These mimic the behavior of molecules like cohesin, which, along with the CTCF protein, stabilize loops which contribute to organizing the genome. By combining 3D Brownian dynamics simulations and 1D exactly solvable nonequilibrium models, we show that diffusive sliding is sufficient to account for the strong bias in favor of convergent CTCF-mediated chromosome loops observed experimentally. We also find that the diffusive motion of multiple slip links along chromatin is rectified by an intriguing ratchet effect that arises if slip links bind to the chromatin at a preferred “loading site.” This emergent collective behavior favors the extrusion of loops which are much larger than the ones formed by single slip links.
spellingShingle Brackley, C
Johnson, J
Michieletto, D
Morozov, A
Nicodemi, M
Cook, P
Marenduzzo, D
Nonequilibrium chromosome looping via molecular slip links
title Nonequilibrium chromosome looping via molecular slip links
title_full Nonequilibrium chromosome looping via molecular slip links
title_fullStr Nonequilibrium chromosome looping via molecular slip links
title_full_unstemmed Nonequilibrium chromosome looping via molecular slip links
title_short Nonequilibrium chromosome looping via molecular slip links
title_sort nonequilibrium chromosome looping via molecular slip links
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