Extensive mutual influences of SMC complexes shape 3D genome folding

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Mammalian genome folding relies on structural maintenance of chromosome (SMC) complexes like cohesin and condensin.
• These complexes coexist on chromatin during the G2-to-M phase transition, a critical period for genome reorganization.
• The precise interactions and coordinated functions of different SMC complexes in genome folding remain largely unknown.

Purpose of the Study:

• To investigate the interplay between cohesin and condensin complexes during mitotic progression.
• To elucidate how these SMC complexes mutually influence each other's function in chromatin organization.
• To understand the orchestration of dynamic genome folding by multiple SMC complexes.

Main Methods:

• Engineered all possible configurations of cohesin and condensin on mitotic chromosomes.
• Analyzed the impact of these configurations on chromatin structure and SMC complex localization.
• Investigated the functional consequences of SMC complex interactions on genome organization.

Main Results:

• Condensin disrupts extrusive cohesin binding at CTCF sites, promoting the disassembly of interphase topologically associating domains (TADs) and loops.
• Extrusive cohesin impedes condensin-mediated chromosome spiralization, while cohesive cohesin antagonizes condensin-mediated longitudinal shortening.
• Cohesive cohesin restricts loop expansion by extrusive cohesin, highlighting distinct roles and interactions among SMC complexes.

Conclusions:

• A three-way interaction among cohesin (extrusive and cohesive) and condensin dynamically modulates chromatin architecture during cell cycle progression.
• Condensin and cohesin exhibit antagonistic and synergistic effects, fine-tuning genome folding during mitosis.
• Cohesive cohesin plays a distinct role, positioning cohesin at CTCF sites but lacking loop-extrusion capacity.