Cohesin acts as a transcriptional gatekeeper by restraining pause–release to promote processive elongation [Micro-C]

We address this paradox by demonstrating that cohesin acts at different stages of transcription in human cells. First, it promotes Pol II promoter recruitment by facilitating enhancer–promoter communication that maintains active promoter chromatin states.

Second, it delays pause release by transiently associating with the transcriptional machinery during the pause–release transition. Kinetic modelling suggests that reduced Pol II recruitment and enhanced pause release have compensatory effects, contributing to minimal changes in steady-state gene expression across genes upon cohesin loss. In contrast, cohesin depletion impairs robust transcriptional induction in response to external stimuli.