Magnetic Polymer Models for Epigenomic Organisation and Phase Separation

Abstract

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.

arXiv commentmain text + SI; Supplementary Movies can be found at https://www2.ph.ed.ac.uk/~dmichiel/MP.html

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Cited by in corpus (8)

• Magnetic Polymer Models for Epigenetics-Driven Chromosome Folding
• Rheology and Viscoelasticity of Proteins and Nucleic Acids Condensates
• Critical Behaviour of Magnetic Polymers in Two and Three Dimensions
• Solution of Disordered Microphases in the Bethe approximation
• Characterization and Efficient Monte Carlo Sampling of Disordered Microphases
• Emergence of compact-disordered phase in a polymer Potts model
• Phase separation in soft repulsive polymer mixtures: foundation and implication for chromatin organization
• Semianalytical solutions of Ising-like and Potts-like magnetic polymers on the Bethe lattice