Aqp5 Is a New Transcriptional Target of Dot1a and a Regulator of Aqp2

摘要: Dot1l encodes histone H3 K79 methyltransferase Dot1a. Mice with deficiency in renal Aqp2-expressing cells (Dot1lAC) develop polyuria by unknown mechanisms. Here, we report that Aqp5 links deletion to through Aqp2. cDNA array analysis revealed and real-time RT-qPCR validated as the most upregulated gene Dot1lAC vs. control mice. protein is barely detectable controls, but robustly expressed kidneys, where it colocalizes The upregulation of coupled reduced association Dot1a dimethyl specific subregions 5′ flanking region In vitro studies IMCD3, MLE-15 293Tcells using multiple approaches including RT-qPCR, luciferase reporter assay, cell surface biotinylation colocalization, co-immunoprecipitation uncovered represses Aqp5. Human AQP5 interacts AQP2 impairs its localization. AQP5/AQP2 complex partially resides ER/Golgi. Consistently, none 15 normal all 17 kidney biopsies from patients diabetic nephropathy. nephropathy, perinuclear expression associated impaired cellular K79. Taken together, these data for first time identify a potential transcriptional target, an Aqp2 binding partner regulator, suggest may contribute polyuria, possibly impairing membrane localization, mice