Dissecting chromatin-mediated gene regulation and epigenetic memory through mathematical modelling

The application of mathematical modelling to chromatin-mediated gene regulation is gaining momentum, but is still surprisingly rare. Here we review examples in which the combination of quantitative experimentation and mathematical modelling has given mechanistic insights into the processes involved. Examples include recruitment of epigenetic regulators, the establishment and maintenance of epigenetic memory, the dynamic cell cycle - dependent changes in chromatin binding of epigenetic regulators, and the contribution of 3D genome architecture to cell identity. The successful combination of theory and experiment requires tractable experimental systems in which quantitative measurements and precise perturbations are possible. The advent of single cell technologies and genome editing presents an unprecedented opportunity for combining quantitative experiments, precise perturbation and modelling, that in future will enable new epigenetic data to be embedded in a coherent theoretical framework.