Systems Biology of Genome Structure and Dynamics

Abstract

Our view of the packed genome inside a nucleus has evolved greatly over the past decade. Aided by novel experimental and bioinformatic analysis techniques and detailed computational models, fundamental insights into the structure and dynamics of chromosomes have been gained. This has revealed that genome organisation has an essential role in controlling genome function during normal growth, cellular differentiation, and stress response, showing that, overall, 3D reorganisation is tightly linked to changes in gene expression. Chromatin, which is composed of DNA and a large number of different chromatin-associated proteins and RNAs, is often chemically modified, in patterns that affect gene expression. It has become clear that this highly interconnected system requires computational simulations to gain an understanding of the underlying system-wide mechanisms. In this review, we describe different modelling approaches that are used to investigate both the linear and spatial arrangement of chromatin. We illustrate how dynamic computer simulations are used to study the mechanisms that control and maintain genome architecture and drive changes in this structure. We focus on models of the dynamics of epigenetic modifications, of protein–DNA interactions, and the polymer dynamics of chromosomes. These approaches provide reliable frameworks to integrate additional biological data; enable accurate, genome-wide predictions; and allow the discovery of new mechanisms.