BRD10 Regulates DZIP1 Localization at the Primary Cilium During Mitral Valvulogenesis

Mitral valve prolapse (MVP) is a common congenital valve disorder that has been linked to defects in primary cilia during cardiac development, yet the mechanisms connecting ciliary regulation to valvulogenesis remain incompletely understood. As DZIP1 is required for ciliogenesis and has been shown to be involved in MVP pathogenesis, we sought to identify interacting partners that may regulate its localization and function. Using an unbiased yeast two-hybrid screen of a human heart cDNA library, we identified BRD10, a previously uncharacterized bromodomain-containing protein, as a DZIP1-interacting partner. Co-immunoprecipitation confirmed the DZIP1-BRD10 interaction and mapped the binding region to a conserved domain containing a putative nuclear localization sequence. RNAscope and immunofluorescence demonstrated that BRD10 and DZIP1 are co-expressed in developing murine valve cells, with BRD10 localizing near the basal body and transition zone of the primary cilium. BRD10 also interacted with acetylated α-tubulin, supporting a relationship with ciliary microtubule structures. Nuclear-cytoplasmic fractionation further showed that BRD10 promotes cytoplasmic enrichment of DZIP1. Together, these findings identify BRD10 as a novel regulator of DZIP1 subcellular localization and suggest that bromodomain-mediated recruitment at the primary cilium may contribute to normal valvulogenesis and developmental mechanisms relevant to MVP.