Mechanisms and Functions of Chromosome Compartmentalization

Active and inactive chromatin are spatially separated in the nucleus. In Hi-C data, this is reflected by the formation of compartments, whose interactions form a characteristic checkerboard pattern in chromatin interaction maps. Only recently have the mechanisms that drive this separation come into view. Here, we discuss new insights into these mechanisms and possible functions in genome regulation. Compartmentalization can be understood as a microphase-segregated block co-polymer. Microphase separation can be facilitated by chromatin factors that associate with compartment domains, and that can engage in liquid-liquid phase separation to form subnuclear bodies, as well as by acting as bridging factors between polymer sections. We then discuss how a spatially segregated state of the genome can contribute to gene regulation, and highlight experimental challenges for testing these structure-function relationships.