Nuclear chromatin patterns: modeling dynamics of intra-chromatin interactions and its impact on structure organization

The description of chromatin organization and its dynamics, at a large scale, are functionally important factors in the genome regulation function. Growing evidence suggests that chromatin within the nucleus has a liquid-like behavior mediated by phase separation into micro-droplets with distinct transcriptional states. The formation and spatial arrangement of chromatin droplets within the nucleus depending on their transcriptional states either active (euchromatin) or inactive (constitutive and facultative heterochromatin) genes are important features of the nuclear architecture. Understating mechanisms that control the dynamics and spatiotemporal regulation of droplets formation is a possible way to elucidate the relationship between nuclear architecture and gene regulation. Here, we introduce a mesoscale liquid model of nucleus (MELON) that incorporates dynamic of interactions between A-B-C chromatin compartments of the nucleus, as well as the affinity between constitutive heterochromatin and Lamina at the nuclear envelope and nucleus deformation. Using MELON framework, we show that phase separation together with surface tension effects and nuclear shape deformation is sufficient for recapitulating large-scale morphology and dynamics of chromatin along the life cycle of cells.