A Model For Chromatin Organization Through Liquid-Liquid Phase Separation

Biomolecular condensates are two- and three-dimensional compartments in eukaryotic cells that concentrate specific collections of proteins and nucleic acids without an encapsulating membrane. Many condensates behave as dynamic liquids, and are believed to form through liquid-liquid phase separation (LLPS) driven by interactions between multivalent macromolecules. Efforts in my lab have recently expanded in a new direction, to understand whether and how LLPS might regulate the organization of chromatin in the eukaryotic cell nucleus. In my talk I will discuss our finding that polynucleosome arrays, which mimic the multivalent chromatin polymer, have an intrinsic capacity to undergo LLPS. Moreover, many factors known to control chromatin organization in cells have parallel effects on phase separated chromatin droplets in vitro, including histone H1, internucleosome spacing and histone tail acetylation. Our data suggest a new framework, based on intrinsic phase separation of the chromatin polymer, to understand the organization and regulation of eukaryotic genomes.