Long-lived memory and dynamics of liquefied chromatin

Chromatin is organized into spatially segregated compartments, referred to as (active) euchromatin and (inactive) heterochromatin. Compartments are thought to be formed by phase separation, which may be facilitated by the underlying linear polymer structure of the genome. However, recent “liquid Hi-C” experiments in which chromosomes are fragmented into tiny segments reveal an hours-long spatial memory that does not rely on large-scale polymer connectivity. To understand the physical mechanisms and dynamics of this memory, we analyze Hi-C genome contact maps and perform polymer molecular dynamics simulations. In a heteropolymer simulation model, we find that strong interactions between inactive chromatin segments can lead to slow melting of inactive compartments, as in experiments. Surprisingly, in Hi-C maps, we find that contacts between segments separated by small genomic distances are maintained despite the fragmentation of the genome. Our model can only reproduce this counterintuitive behavior when such contacts are maintained by another cell nuclear structure, such as the lamina. Thus, while phase separation may globally compartmentalize chromatin, it is insufficient to dictate short-distance contacts, which instead may be maintained by specific, long-lived interactions.