Recent studies have uncovered several intermediate filament proteins, previously thought to be exclusively cytoplasmic, that also localise and act inside the cell nucleus. One such intermediate filament protein is keratin 17 (K17); however, its function in the nucleus remains mostly obscure. Now, Pierre A. Coulombe and colleagues (Jacob et al., 2020) report a role for K17 in regulating nuclear shape and chromatin structure. They first observe that loss of K17 leads to altered nuclear morphology – KRT17 knockout keratinocyte cell lines and primary cells displayed larger nuclear area, decreased sphericity and increased total surface area compared with control cells. Nuclear morphology could be restored when re-expressing wild-type K17 but not when the nuclear localisation signal was mutated, confirming that the nuclear pool of K17 is responsible for regulating nuclear shape. To further explore how K17 affects nuclear morphology, the authors carried out unbiased and biased proteomic screens and, among the enriched K17 interactors, found several nuclear envelope components, which might be accountable for the nuclear shape changes. Finally, to assess whether K17-mediated nuclear shape changes are coupled to changes in chromatin structure and gene expression, the authors probed for several histone marks associated with active euchromatin and found that their levels were globally reduced in the KRT17 knockout. Together, these results identify K17 as an unexpected novel player in the regulation of nuclear organisation.
