ERR? coordinates a transcriptional program of mitochondrial and renal reabsorptive functions implicated in kidney disease [ChIP-seq]

Here we show that estrogen-related receptor ? (ERR?) is an essential transcriptional coordinator of both renal mitochondrial and reabsorptive functions. ERR? is highly and specifically expressed in the RECs, and its expression correlates with kidney function in humans. We generated REC-ERR? KO mice which developed severe renal mitochondrial and reabsorptive dysfunction and fluid-filled cysts. Transcriptome and cistrome analysis revealed that ERR? directly regulates mitochondrial metabolism and renal reabsorption. ChIP-reChIP-Seq studies further suggest that ERR? employs a distinct mechanism to regulate renal reabsorption genes through functional cooperation with hepatic nuclear factor 1 beta (HNF1ß), mutations of which cause strikingly similar renal dysfunction and cysts in humans and animals. Together these findings reveal a novel role for ERR? in simultaneously coordinating a transcriptional program for renal energy production via mitochondria and energy consumption to perform reabsorptive functions required for normal kidney function Overall design: Identification of ERRg, HNF1b, and ERRg-HNF1b cobound sites in C57Bl6/J mouse kidneys