Figure 5: Current models of interphase chromosome organization through integrated activity of multiple mechanisms.

Schematic depiction of interphase chromosome conformation in eukaryotes as the combined and integrated result of multiple folding mechanisms. The chromosome is a worm-like chain that phase separates in distinct compartments (A/B compartments or finer subcompartments) driven by homotypic affinities. Tethering of domains to sub-nuclear structures such as the nuclear lamina, the nucleolus, or nuclear bodies including speckles, leads to positioning of loci and chromosomes at specific nuclear locations. Topological contraints prevent mixing in interphase but self-entanglements are formed in mitosis, facilitating full and fast compaction. At the scale of hundreds of Kb, loop extrusion, guided by cis elements that determine loading, unloading, and blocking (CTCF) of loop extruders, and with extensive interplay with other folding mechanisms, including compartmentalization, adds an additional layer of chromosome folding.