Nonequilibrium Chromosome Looping via Molecular Slip Links

CA Brackley and J Johnson and D Michieletto and AN Morozov and M Nicodemi and PR Cook and D Marenduzzo, PHYSICAL REVIEW LETTERS, 119, 138101 (2017).

DOI: 10.1103/PhysRevLett.119.138101

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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