Cohesin Transmission Across Mitosis Ensures Transcription Reestablishment Through Cdk9-mediated Activation of RNA Pol II [RNA-seq]

ABSTRACT: In this study we combined selective labelling and acute depletion of mitotic inherited cohesin during the telophase-G1 passage to interrogate the functional relevance of cohesin on post-mitotic transcriptional reactivation. Our results tracking pre-mitotic labelled cohesin demonstrate transmission of both cohesinSTAG1 and cohesinSTAG2 complexes through mitosis, the first one showing faster reassociation with chromatin. Nipbl and Wapl, although using opposite mechanisms, both play an essential role on cohesin inheritance and reuse. Remarkably, our labelling strategy allowed us to differentially mark and track mitotic-inherited and new-translated cohesin. Our findings demonstrate that the large fraction of functional-chromatin bound cohesin early in G1 corresponds to the mitotic-transmitted fraction. This pool is sequentially displaced by new-translated cohesin at the G1-S transition. Our results reveal that recycled cohesin preferentially localizes to active chromatin, especially promoters, enhancers, and CTCF sites, and that this enrichment partially relies on the bookmarking factor TBP. Nascent transcriptomic analysis under acute depletion of Rad21 reveal cohesin-dependent transcriptional regulation of hundreds of genes enriched on tissue growth and development categories. We observed selective disruption of phosphor-ser2 RNAPol2 variant under Rad21 depletion in down-regulated genes, which support that cohesin facilitates promoter-paused to active-elongating RNAPol2 transition. Indeed, our results reveal Rad21-Cdk9 direct interaction and that Rad21/cohesinSTAG1 ensures proper Cdk9 function/chromatin levels early in G1. Overall, our findings support a mechanism based on the direct interaction of mitotic-inherited cohesin with the promoter of a specific set of genes to facilitate Cdk9-mediated activation of RNAPol2. In conclusion, our findings evidence that the mitotic transmission of cohesin ensures full post-mitotic transcriptional recovery and, importantly, reveal a locus-specific mechanism linking cohesin to RNAPol2 activation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE308493 | GEO | 2026/09/01

REPOSITORIES: GEO