Multiscale modelling of chromatin organisation: Resolving nucleosomes at near-atomistic resolution inside genes

Abstract

The three-dimensional organisation of the genome modulates biological processes and is, in turn, transformed by the activity in the nucleus. Not surprisingly, understanding how the genome operates requires uncovering the fundamental biophysical and molecular mechanisms that establish and regulate its organisation. Genome organisation starts with the formation of chromatin: a polymer of nucleoprotein complexes, termed nucleosomes, that carry variable chemical signatures according to their biological context. The physicochemical heterogeneity of chromatin, the stochastic organisation it fosters, and the multiscale nature of genome organisation pose great technical challenges. Excitingly, advances in imaging and molecular biology techniques are addressing chromatin organisation at increasing resolutions. In tandem, computer models are testing and postulating hypotheses, interpreting the experimental data, and linking molecular properties of nucleosomes to the mesoscale organisation of chromatin. We discuss how coarse-grained models at varying resolutions are expanding our mechanistic understanding of chromatin organisation, and the challenges still remaining in the field.