RNA polymerase II is required for spatial chromatin reorganization following exit from mitosis

Mammalian chromosomes are three-dimensional entities shaped by converging and opposing forces. Mitotic cell division induces marked chromosome condensation, but following reentry into the G(1) phase of the cell cycle, chromosomes reestablish their interphase organization. Here, we tested the role of RNA polymerase II (RNAPII) in this transition using a cell line that allows its auxin-mediated degradation. In situ Hi-C showed that RNAPII is required for both compartment and loop establishment following mitosis. RNAPs often counteract loop extrusion, and in their absence, longer and more prominent loops arose. Evidence from chromatin binding, super-resolution imaging, and in silico modeling allude to these effects being a result of RNAPII-mediated cohesin loading upon G(1) reentry. Our findings reconcile the role of RNAPII in gene expression with that in chromatin architecture.

Automated summary

The study reveals that RNA polymerase II plays a critical role in the establishment of chromosome compartments and loops following mitosis, with its absence leading to the formation of longer and more prominent loops. This highlights the importance of RNA polymerase II in chromatin architecture post-mitosis.