The polymer model of constitutive heterochromatin

Chromatin structure is regulated on multiple levels, yet the mechanisms by which this occurs are not yet understood. In recent studies, phase separation has been shown to play a key role in a wide range of cellular processes including, some features of chromatin organization. We develop a simple model containing spherical particles and a single chain polymer to represent proteins and chromatin. By examining the interplay between protein-protein and protein-chromatin interactions, we investigate the constitutive-heterochromatin(c-Het) organization through liquid-liquid phase separation and/or polymer-polymer phase separations mechanisms. We construct a phase diagram for a multivalent protein that includes globule polymer-stable protein droplet, globule polymer-unstable protein droplet, coil polymer-unstable droplet, and coil-like polymer-stable droplet. We show that c-Het resides in the globule polymer-unstable protein droplet phase, in which the protein condensate forms due to interactions between the proteins and the polymer. In contrast to a standard phase separating system, both our analytical and simulations results show that the total protein concentration in the system controls the protein concentration in a droplet. Furthermore, the transition from the compact polymer to the coil state is accompanied by hysteresis: this suggests that the c-Het is metastable, and that the transition from regular c-Het domains to disturbed domains is likely irreversible. Finally, we find that protein-protein interactions are a key factor contributing to the mechanical properties of chromatin domains, shedding light on the nature of chromatin-protein condensates in the nucleus.