Cohesin acetylation and ATPase activity control cohesion and loop architecture through distinct mechanisms

ABSTRACT: Cohesin is a conserved protein complex that mediates sister chromatid cohesion, chromosome condensation, gene regulation, and DNA repair. These processes rely on cohesin’s ability to tether sister chromatids and form chromatin loops, which depend on cohesin’s ATP hydrolysis activity and Eco1-mediated acetylation of two lysines (K112 and K113 in budding yeast) in its Smc3 subunit. How cohesin’s ATPase activity and acetylation integrate to control cohesin functions remains poorly understood. To address this, we analyzed chromatin architecture in yeast mutants with altered cohesin acetylation and/or ATPase activity. We find that acetylation of either K112 or K113 is sufficient to form a wild-type pattern of loops anchored at cohesin-associated regions (CARs), whereas loss of acetylation at both residues abolishes positioned loops, indicating that acetylation of either lysine is sufficient for loop positioning. We found that a cohesin acetylation mutant lacking the tethering activity required for cohesion was able to form loops similar to wild type, while cohesion-competent mutants lacked positioned loops. Together, these results suggest that the activities required for cohesion and loop formation are mechanistically separable, arguing against loop formation through passive loop capture. Moreover, a mutant with reduced ATPase activity showed a wild-type loop profile, indicating that lowering ATPase activity does not dictate loop size or positioning. However, hyper-ATPase mutants exhibited an accumulation of positioned loops, suggesting that ATPase levels contribute to loop processivity. Together, our findings reveal a multilayered regulatory logic in which acetylation fine-tunes ATPase output and cohesin functions to shape genome architecture.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE310515 | GEO | 2026/04/09

REPOSITORIES: GEO