A role for condensin-mediator interaction in mitotic chromosome organization.

Condensin organizes eukaryotic genomes into three-dimensional (3D) chromosome architectures that support accurate chromosome segregation during mitosis. However, the molecular mechanisms underlying this organization remain unclear. Here, we identify a previously unrecognized interaction between the condensin subunit Cnd1 and the mediator subunit Pmc4 in fission yeast, Schizosaccharomyces pombe. We characterize a condensin mutation, cnd1-K658E, which disrupts this interaction and observe that it impairs the formation of condensin-mediated chromatin domains during mitosis, resulting in chromosome segregation defects. This condensin-mediator interaction facilitates condensin recruitment to highly transcribed genes and mitotically activated genes, the latter of which demarcate condensin-mediated domains. Moreover, 1,6-hexanediol treatment and Pmc4 mediator depletion impair expression of mitotically activated genes, diminish condensin enrichment at those boundary genes, and disrupt domain boundaries, suggesting that mediator contributes to mitotic gene expression and chromosome architecture via phase separation. Together, these results reveal a mechanism by which mitotic gene expression patterns shape condensin-mediated chromosome architecture to ensure faithful chromosome segregation.