Nonequilibrium Theory of Epigenomic Microphase Separation in the Cell Nucleus

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.

arXiv commentTo appear in PRL; The quality of figures in this version is downgraded to comply with the arXiv storage limits

References in corpus (17)

• Physics of Active Emulsions
• Cluster phases and bubbly phase separation in active fluids: Reversal of the Ostwald process
• Non-equilibrium chromosome looping via molecular slip-links
• Small activity differences drive phase separation in active-passive polymer mixtures
• The physics of epigenetics
• Ephemeral protein binding to DNA shapes stable nuclear bodies and chromatin domains
• Shaping Epigenetic Memory via Genomic Bookmarking
• Stress granule formation via ATP depletion-triggered phase separation
• Bifurcation in epigenetics: implications in development, proliferation and diseases
• Phase diagram of magnetic polymers
• Metastable States in Spin Glasses and Disordered Ferromagnets
• Magnetic Polymer Models for Epigenetics-Driven Chromosome Folding
• Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1) binding to nucleosomal arrays
• Epigenetic Transitions and Knotted Solitons in Stretched Chromatin
• Late stages of coarsening in model C
• Dynamical Scaling and Phase Coexistence in Topologically-Constrained DNA Melting
• Statistical mechanics of random graphs

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