Magnetic Polymer Models for Epigenomic Organisation and Phase Separation

TL;DR

This paper introduces a magnetic polymer model to understand how epigenetic marks and 3D genome folding interact, revealing phase transitions and the role of non-equilibrium processes in stabilizing chromatin compartments.

Contribution

It presents a novel magnetic polymer framework combining mean field theory and simulations to explore epigenetic spreading and nuclear compartmentalization.

Findings

First order transition in epigenetic spreading

Micro-phase separation is thermodynamically unstable in equilibrium

Non-equilibrium ATP-driven switching stabilizes chromatin compartments

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.