The BRG1/BRM-associated factor (BAF) complex is a multi-subunit chromatin-remodeling complex that carries out specialised functions via the incorporation of accessory subunits. The double-PHD fingers 3 (DPF3) protein is one such subunit that binds acetylated or methylated histones on chromatin, acting as a histone reader. Now (Verrillo et al., 2024), Denis Mottet and colleagues reveal unexpected and moonlighting functions for DPF3. They show that in cell line models, DPF3 localizes to centriolar satellites in interphase and is spatiotemporally located in the centrosome, spindle midzone/bridging fibre area and midbody during mitosis. In addition, depletion of DPF3 results in kinetochore-fibre (K-fibre) instability, less stable kinetochore–microtubule attachment and defects in chromosome alignment at the metaphase plate, with subsequent mitotic arrest, genomic instability and apoptosis. Furthermore, immunostaining of hTERT-RPE-1 cells grown in serum-deprived conditions, so that they assemble a primary cilium, shows that DPF3 localises in centriolar satellites at the basal body of primary cilium. Interestingly, knockdown of DPF3 results in impaired primary ciliogenesis at the initial step of axoneme extension. Overall, this study identifies a surprising new cellular localisation and unexpected function of DFP3 in mitosis and ciliogenesis, and places DPF3 on the growing list of chromatin-associated proteins that moonlight as mitotic regulators.
