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

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.