title: Systems-level analysis reveals selective regulation of Aqp2 gene expression by vasopressin.
abstract: Vasopressin-mediated regulation of renal water excretion is defective in a variety of water balance disorders in humans. It occurs in part through long-term mechanisms that regulate the abundance of the aquaporin-2 water channel in renal collecting duct cells. Here, we use deep DNA sequencing in mouse collecting duct cells to ask whether vasopressin signaling selectively increases Aqp2 gene transcription or whether it triggers a broadly targeted transcriptional network. ChIP-Seq quantification of binding sites for RNA polymerase II was combined with RNA-Seq quantification of transcript abundances to identify genes whose transcription is regulated by vasopressin. (View curated dataset at https://helixweb.nih.gov/ESBL/Database/Vasopressin/). The analysis revealed only 35 vasopressin-regulated genes (of 3659) including Aqp2. Increases in RNA polymerase II binding and mRNA abundances for Aqp2 far outstripped corresponding measurements for all other genes, consistent with the conclusion that vasopressin-mediated transcriptional regulation is highly selective for Aqp2. Despite the overall selectivity of the net transcriptional response, vasopressin treatment was associated with increased RNA polymerase II binding to the promoter proximal region of a majority of expressed genes, suggesting a nearly global positive regulation of transcriptional initiation with transcriptional pausing. Thus, the overall net selectivity appears to be a result of selective control of transcriptional elongation.
authors.affiliation: Epithelial Systems Biology Laboratory, NHLBI, National Institutes of Health, Bethesda, MD 20892-1603, USA.
authors.forename: Pablo C
authors.initials: PC
authors.lastname: Sandoval
authors.affiliation: Epithelial Systems Biology Laboratory, NHLBI, National Institutes of Health, Bethesda, MD 20892-1603, USA.
authors.forename: J'Neka S
authors.initials: JS
authors.lastname: Claxton
authors.affiliation: Epithelial Systems Biology Laboratory, NHLBI, National Institutes of Health, Bethesda, MD 20892-1603, USA.|National Cancer Center, Goyang Gyeonggi-do, Korea.
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Epithelial Systems Biology Laboratory, NHLBI, National Institutes of Health, Bethesda, MD 20892-1603, USA.
authors.forename: Fahad
authors.initials: F
authors.lastname: Saeed
authors.affiliation: Epithelial Systems Biology Laboratory, NHLBI, National Institutes of Health, Bethesda, MD 20892-1603, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Hoffert
authors.affiliation: Epithelial Systems Biology Laboratory, NHLBI, National Institutes of Health, Bethesda, MD 20892-1603, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Knepper
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism*; D065667:Renal Elimination; D015398:Signal Transduction; D014667:Vasopressins / Q000378:metabolism
chemical_list: C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D014667:Vasopressins; D012319:RNA Polymerase II