Cohesin removal reprograms gene expression upon mitotic entry

Entering mitosis, the genome is restructured to facilitate chromosome segregation, accompanied by dramatic changes in gene expression. However, the mechanisms that underlie mitotic transcriptional regulation are unclear. In contrast to transcribed genes, centromere regions retain transcriptionally active RNA Polymerase II (RNAPII) in mitosis. Here, we demonstrate that chromatin-bound cohesin is sufficient to retain RNAPII at centromeres while WAPL-mediated removal of cohesin during prophase is required for RNAPII dissociation from chromosome arms. Failure to remove cohesin from chromosome arms results in a failure to release elongating RNAPII and nascent transcripts from mitotic chromosomes and dramatically alters gene expression. We propose that prophase cohesin removal is the key step in reprogramming gene expression as cells transition from G2 to mitosis, and is temporally coupled with chromosome condensation to coordinate chromosome segregation with changes in gene expression.\n\nHighlightsO_LIMitotic centromere transcription requires cohesin\nC_LIO_LICohesin removal releases elongating RNA Pol II and nascent RNA from chromatin\nC_LIO_LIThe prophase pathway reprograms gene expression during mitosis\nC_LI