Extensive mutual influences of SMC complexes shape 3D genome folding

ABSTRACT: Mammalian genomes are folded by the distinct actions of SMC complexes which include the chromatin loop-extruding cohesin, the sister-chromatid cohesive cohesin, and the mitotic chromosome-associated condensins 1-3. While these complexes function at different stages of the cell cycle, they co-exist on chromatin during the G2/M-phase transition, when genome structure undergoes a dramatic reorganization 1,2. Yet, how distinct SMC complexes affect each other and how their mutual interplay orchestrates the dynamic folding of 3D genome remains elusive. Here, we engineered all possible cohesin/condensin configurations on mitotic chromosomes to delineate the concerted, mutually influential action of SMC complexes. We find that: (i) Condensin disrupts extrusive-cohesin binding at CTCF sites, thereby promoting the disassembly of interphase TADs and loops during mitotic progression. Conversely, extrusive-cohesin impedes condensin mediated mitotic chromosome spiralization. (ii) Condensin diminishes cohesive-cohesin peaks and, conversely, cohesive-cohesin antagonizes condensin-mediated mitotic chromosome longitudinal shortening. Co-presence of extrusive- and cohesive-cohesin synergizes these effects and dramatically inhibits mitotic chromosome condensation. (iii) Extrusive-cohesin positions cohesive-cohesin at CTCF binding sites. However, cohesive-cohesin by itself cannot be arrested by CTCF molecules, is insufficient to establish TADs or loops and lacks loop extrusion capacity, implying non-overlapping function with extrusive-cohesin. (iv) Cohesive-cohesin restricts extrusive-cohesin mediated chromatin loop expansion. Collectively, our data describe a comprehensive three-way interplay among major SMC complexes that dynamically sculpts chromatin architecture during cell cycle progression.

ORGANISM(S): Mus musculus

PROVIDER: GSE269952 | GEO | 2024/12/21

REPOSITORIES: GEO