11 / 2024-08-15 16:26:56

Decoding 3D genome folding principles using mitotic chromosomes

condensin,cohesin,mitosis,chromosome

During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we co-depleted condensin I and II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac. Constitutive heterochromatin gradually self-aggregated and co-compartmentalized with facultative heterochromatin, contrasting with their separation during interphase. Notably, some cis-regulatory element contacts became apparent even in the absence of CTCF/cohesin mediated structures. HP1 proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M- to G1-phase in the combined absence of HP1a, HP1b and HP1g, re-established constitutive heterochromatin compartments normally. In sum, “clean-slate” condensin-deficient mitotic chromosomes illuminate forces of genome compartmentalization not revealed in interphase cells.