Chromatin Compartmentalization can Emerge from Crosslinks, Motors, and Nuclear Deformability

During interphase, a typical cell nucleus features spatial compartmentalization of more transcriptionally active euchromatin and less transcriptionally active heterochromatin domains. Euchromatin predominantly occupies the nuclear interior, while heterochromatin is positioned at the nuclear periphery and is approximately 50% more dense than euchromatin. Peripheral chromatin organization can be further modulated by the nuclear lamina, which is itself a deformable structure. A number of biophysical mechanisms for compartmentalization have been proposed, including stronger, attractive interactions between heterochromatin regions (as compared to euchromatin regions) driving phase separation as well as a combination of extensile motors and hydrodynamic interactions. To further elucidate the physical principles driving the self-organization of heterochromatin-euchromatin compartmentalization within deformable nuclei, we develop a model of an active, crosslinked polymer tethered to a polymeric lamina shell. Contractile motors, the deformability of the shell, and the distribution of crosslinks all play pivotal roles in this compartmentalization. We find that heterochromatin is effectively trapped by deformations of the shell and that trapping is reinforced by linkages to the lamina shell. We also study the effects of cytoskeletal activity on the spatial compartmentalization. Our findings reveal the interplay between nuclear mechanics and differential chromatin distribution.