bioRxiv | 2019
Mesoscale liquid model of chromatin recapitulates large-scale organization of eukaryotic cell nuclei
Abstract
The nuclear envelope segregates the genome of eukaryota from the cytoplasm. Within nucleus chromatin is further compart-mentalized into architectures that change throughout lifetime of the cell. Epigenetic patterns along the chromatin polymer strongly correlate with chromatin compartmentalization and, accordingly, also change during cell life cycle and at differentiation. Recently, it has been suggested that sub-nuclear chromatin compartmentalization might result from a process of liquid-liquid phase separation orchestrated by the epigenetic marking and operated by proteins that bind to chromatin. Here, we translate these observations into a diffuse interface model of chromatin, which we named Mesoscale Liquid mOdel of Nucleus (MELON). Using this streamlined continuum model of the genome, we study the large-scale rearrangements of chromatin that happen at different stages of the growth and senescence of the cell, and during nuclear inversion events. Particularly, we investigate the role of droplet diffusion, fluctuations, and heterochromatin-lamina interactions during nuclear remodeling. Our results indicate that the physical process of liquid-liquid phase separation, together with surface effects is sufficient to recapitulate much of the large-scale morphology and dynamics of chromatin along the life cycle of cells.