Liquid-liquid phase separation driven organization of nuclear chromatin domains

Chromatin of eukaryotic cells folds within few micrometers of nuclear space while still retaining dynamism and accessibility needed for function. Latest experiments have revealed a liquid like behavior of chromatin manifested in epigenetically mediated phase separation into micro-droplets with distinct transcriptional states. Motivated by these experiments we have devised a mesoscale liquid like model of nucleus (MELON) with chromatin states resolved as a viscoelastic fluid fields of type A and B corresponding to transcriptionally active and silent states. The model allows direct comparison with imaging experiments of different cell lines and during various stages in cell cycle. Using MELON framework, we investigate the roles of chromatin droplet diffusion, fluctuations and impact of phase separation kinetics on non-equilibrium processes of growth and inversion. We show that ideas based on classical theories of nucleation and phase separation can have a broad predictive power in capturing several salient features of intra-nuclear chromatin dynamics.