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Magnetic Polymer Models for Epigenomic Organisation and Phase Separation

By Davide Colì, Davide Michieletto, Davide Marenduzzo, Enzo Orlandini

Posted 30 Jul 2018
bioRxiv DOI: 10.1101/379941

The genetic instructions stored in the genome require an additional layer of information to robustly determine cell fate. This additional regulation is provided by the interplay between chromosome-patterning biochemical ("epigenetic") marks and three- dimensional genome folding. Yet, the physical principles underlying the dynamical coupling between three-dimensional genomic organisation and one-dimensional epigenetic patterns remain elusive. To shed light on this issue, here we study by mean field theory and Brownian dynamics simulations a magnetic polymer model for chromosomes, where each monomer carries a dynamic epigenetic mark. At the single chromosome level, we show that a first order transition describes the unlimited spreading of epigenetic marks, a phenomenon that is often observed in vivo. At the level of the whole nucleus, experiments suggest chromosomes form micro-phase separated compartments with distinct epigenetic marks. We here discover that for a melt of magnetic polymers such a morphology is thermodynamically unstable, but can be stabilised by a non-equilibrium and ATP-mediated epigenetic switch between different monomer states.

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