Interplay of Loop Extrusion, Compartmentalization and Global Chromosome Dynamics Across Conditions and the Cell Cycle

The most widely known and most striking aspect of chromosome dynamics is their strong compaction for cell division. Thereafter, they are released into more extended conformations, and assume a high degree of spatial organization. Prominent examples are: (i) local interaction domains (TADs) due to active extrusion of chromatin loops, (ii) segregation of active and inactive sections into distinct spatial compartments, likely due to a phase separation process, and (iii) chromosome territoriality, i.e. a chromosomes spatial extent is far smaller than the corresponding equilibrium polymer coil.

We explore to what extent comparatively simple polymer physics explains chromosome organization, and where its shortcomings indicate more specific, biological mechanisms. Specifically, we show that the interplay loop extrusion and compartmentalization is a crucial aspect of interphase organization: several mutants targeting the loop extrusion machinery also affect compartmentalization. (PNAS 115, E6697). Furthermore, we investigate the joint dynamics of loop extrusion, compartmentalization, and chromosome intermingling during entry into and exit from mitosis.