Nonequilibrium Theory of Epigenomic Microphase Separation in the Cell Nucleus

TL;DR

This paper develops a non-equilibrium physical theory explaining how epigenetic marks influence genome organization in the cell nucleus, highlighting the importance of non-equilibrium processes in stabilizing microphase-separated domains.

Contribution

It introduces a novel non-equilibrium model coupling epigenetic and genome densities, explaining nuclear organization beyond equilibrium assumptions.

Findings

Equilibrium models fail to match experimental data.

Non-equilibrium processes stabilize epigenomic microdomains.

The theory suggests biophysical origins for these non-equilibrium terms.

Abstract

Understanding the spatial organisation of the genome in the cell nucleus is one of the current grand challenges in biophysics. Certain biochemical -- or epigenetic -- marks that are deposited along the genome are thought to play an important, yet poorly understood, role in determining genome organisation and cell identity. The physical principles underlying the interplay between epigenetic dynamics and genome folding remain elusive. Here we propose and study a theory that assumes a coupling between epigenetic mark and genome densities, and which can be applied at the scale of the whole nucleus. We show that equilibrium models are not compatible with experiments and a qualitative agreement is recovered by accounting for non-equilibrium processes which can stabilise microphase separated epigenomic domains. We finally discuss the potential biophysical origin of these terms.