Nonequilibrium Theory of Epigenomic Microphase Separation in the Cell Nucleus

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.

Statistical Mechanics: A Tale of Two Theories

There are two theoretical approaches in statistical mechanics, one associated with Boltzmann and the other with Gibbs. The theoretical apparatus of the two approaches offer distinct descriptions of the same physical system with no obvious way to translate the concepts of one formalism into those of the other. This raises the question of the status of one approach vis-à-vis the other. We answer this question by arguing that the Boltzmannian approach is a fundamental theory while Gibbsian statistical mechanics (GSM) is an effective theory, and we describe circumstances under which Gibbsian calculations coincide with the Boltzmannian results. We then point out that regarding GSM as an effective theory has important repercussions for a number of projects, in particular attempts to turn GSM into a nonequilibrium theory.