Abstract
Phase separation is emerging as a paradigm to explain the self-assembly and organization of membraneless bodies in the cell. Recent advances show that this principle also extends to nucleoprotein complexes, including DNA-based structures. We discuss here recent observations on the role of phase separation in genome organization across the evolutionary spectrum from bacteria to mammals. These findings suggest that molecular interactions amongst DNA-binding proteins evolved to form a variety of biomolecular condensates with distinct material properties that affect genome organization and function. We suggest that phase separation contributes to genome organization across evolution and that the resulting phase behavior of genomes may underlie regulatory mechanisms and disease.