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One of the most important problems in development is how epigenetic domainscan be first established, and then maintained, within cells. To address thisquestion, we propose a framework which couples 3D chromatin folding dynamics,to a "recolouring" process modelling the writing of epigenetic marks. Becausemany intra-chromatin interactions are mediated by bridging proteins, weconsider a "two-state" model with self-attractive interactions between twoepigenetic marks which are alike (either active or inactive). This modeldisplays a first-order-like transition between a swollen, epigeneticallydisordered, phase, and a compact, epigenetically coherent, chromatin globule.If the self-attraction strength exceeds a threshold, the chromatin dynamicsbecomes glassy, and the corresponding interaction network freezes. By modifyingthe epigenetic read-write process according to more biologically-inspiredassumptions, our polymer model with recolouring recapitulates theultrasensitive response of epigenetic switches to perturbations, and accountsfor multi-domain conformations, strikingly similar to thetopologically-associating-domains observed in eukaryotic chromosomes.

A Polymer Model with Epigenetic Recolouring Reveals a Pathway for the de novo Establishment and 3D Organisation of Chromatin Domains