Background: WDR5 is a protein known for its role in the epigenetic control of gene expression. Results: During cytokinesis, WDR5 resides at the midbody in the absence of chromatin and promotes normal abscission. Conclusion: WDR5 is a midbody component and regulates the final steps of cytokinesis. Significance: WDR5 may have additional functions and binding partners outside of the cell nucleus.

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Cytokinesis, the physical separation of two dividing cells, occurs at the midbody and affects the growth and development of all organisms. As the final step of cytokinesis, abscission requires membrane fission and cytoskeletal rearrangement at a specific midbody region called the secondary ingression. Here, we report that histone H3 lysine 4 methytransferase (H3K4MT) subunits reside at the midbody. Knockdown of individual H3K4MT subunits increases the incidence of multinucleated cells, slows cell proliferation, and impairs cytokinesis at the abscission step. Further investigation shows that the abscission delay is due to slower formation of secondary ingressions in the knockdown cells. Importantly, the midbody microtubules in H3K4MT knockdown cells display enhanced resistance to depolymerization by nocodazole and the abscission defect in these cells can be partially rescued by drug‐induced microtubule disassembly. We propose that a midbody‐localized H3K4MT complex or subcomplex promotes abscission, at least partially, by facilitating midbody microtubule disassembly. Grant Funding Source: 5R21‐MH086853‐02