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Non-equilibrium chromosome looping via molecular slip-links

View ORCID ProfileC. A. Brackley, J. Johnson, D. Michieletto, View ORCID ProfileA. N. Morozov, View ORCID ProfileM. Nicodemi, P. R. Cook, D. Marenduzzo
doi: https://doi.org/10.1101/095992
C. A. Brackley
1SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK
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  • ORCID record for C. A. Brackley
J. Johnson
1SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK
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D. Michieletto
1SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK
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A. N. Morozov
1SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK
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M. Nicodemi
2Dipartimento di Fisica, Universita’ di Napoli Federico II, INFN Napoli, CNR, SPIN, Complesso Universitario di Monte Sant’Angelo, 80126 Naples, Italy
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P. R. Cook
3Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
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D. Marenduzzo
1SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK
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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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 21, 2016.
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Non-equilibrium chromosome looping via molecular slip-links
C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, D. Marenduzzo
bioRxiv 095992; doi: https://doi.org/10.1101/095992
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Non-equilibrium chromosome looping via molecular slip-links
C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, D. Marenduzzo
bioRxiv 095992; doi: https://doi.org/10.1101/095992

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