Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the kidney, water reabsorption is mainly regulated by the binding of arginine vasopressin to vasopressin type 2 (V2) receptors. These receptors are expressed selectively in principal cells of the collecting ducts. To identify molecular mechanisms responsible for the cell-specific expression of the V2 receptor, we have analyzed the proximal promoter of the corresponding gene. We report the identification of a 33-bp enhancer [collecting duct tissue-specific element 1 (CSE1)] that induced high levels of expression of the luciferase reporter gene in three collecting duct cell lines, but not in other renal cell lines. In gel shift assays, CSE1 bound a DNA-binding protein expressed selectively in collecting duct cell lines, and a 7-bp mutation, which abolished the activity of CSE1 in transient transfection experiments, also abolished the binding of this protein. Furthermore, decoy experiments performed using CSE1 showed that this sequence was involved not only in the expression of a construct containing 4.2 kb of the V2 receptor proximal promoter, but also in the expression of the endogenous V2 receptor gene. CSE1 appears to act mostly by counteracting the inhibitory effects of a strong ubiquitous repressor element that we called CIE1. Collectively, these results identify the first functional collecting duct-specific cis-acting element.
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PMID:Identification of a short cis-acting element in the human vasopressin type 2 receptor gene which confers high-level expression of a reporter gene specifically in collecting duct cells. 1104 82

In eukaryotic nuclei, genomic DNA is compacted with histone and nonhistone proteins into a dynamic polymer termed chromatin. Reorganization of chromatin structure through histone modifications, the action of chromatin factors, or DNA methylation, can profoundly change gene expression. These epigenetic modifications allow heritable and potentially reversible changes in gene functioning to occur without altering the DNA sequence, thus extending the information potential of the genetic code. This review provides an introduction to epigenetic concepts for renal investigators and an overview of our work detailing an epigenetic pathway for aldosterone signaling and the control of epithelial Na(+) channel-alpha (ENaCalpha) subunit gene expression in the collecting duct. This new pathway involves a nuclear repressor complex, consisting of histone H3 Lys-79 methyltransferase disruptor of telomeric silencing-1a (Dot1a), ALL1 fused gene from chromosome 9 (Af9), a sequence-specific DNA-binding protein that binds the ENaCalpha promoter, and potentially other nuclear proteins. This complex regulates targeted histone H3 Lys-79 methylation of chromatin associated with the ENaCalpha promoter, thereby suppressing its transcriptional activity. Aldosterone disrupts the Dot1a-Af9 interaction by serum- and glucocorticoid-induced kinase-1 phosphorylation of Af9, and inhibits Dot1a and Af9 expression, resulting in histone H3 Lys-79 hypomethylation at specific subregions, and derepression of the ENaCalpha promoter. The Dot1a-Af9 pathway may also be involved in the control of genes implicated in renal fibrosis and hypertension.
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PMID:Epigenetics and the control of epithelial sodium channel expression in collecting duct. 1881 87