Role of Liquid-Liquid Phase Separation in Organization and Regulation of Chromatin

Genomic DNA is densely compacted in the nucleus of eukaryotic cells into chromatin. However, mechanisms that regulate the assembly and compaction of the genome remain unclear. Here we employ atomistic simulations to study how histone tail-driven interactions drive liquid-liquid phase separation (LLPS) of archetypal DNA-histone mixtures, resulting in formation of mesoscale condensates. The role of histones H1, H2a, H2b, H3 and H4 are individually explored under a range of physiological salt concentrations. Histone H1 is found to play a critical role in chromatin organization by promoting LLPS, denser compaction and slower dynamics within the condensates. Electrostatic interactions are found to be the primary driving force behind condensate formation and consequently histone acetylation is found to inhibit LLPS. We construct phase diagrams based on Droplet density and Shannon entropy calculations, wherein distinct regimes can be identified based on histone concentrations. The spatial organization and dynamics of the droplets are investigated as a function of histone concentrations, DNA chain length and salt concentration.