The Forkhead Transcription Factor Foxi1 Is a Master Regulator of Vacuolar H\(^+\)-ATPase Proton Pump Subunits in the Inner Ear, Kidney and Epididymis

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The Forkhead Transcription Factor Foxi1 Is a Master Regulator of Vacuolar H\(^+\)-ATPase Proton Pump Subunits in the Inner Ear, Kidney and Epididymis

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dc.contributor.author Vidarsson, Hilmar
dc.contributor.author Westergren, Rickard
dc.contributor.author Heglind, Mikael
dc.contributor.author Blomqvist, Sandra Rodrigo
dc.contributor.author Enerbäck, Sven
dc.contributor.author Breton, Sylvie
dc.date.accessioned 2011-11-01T14:59:34Z
dc.date.issued 2009
dc.identifier.citation Vidarsson, Hilmar, Rickard Westergren, Mikael Heglind, Sandra Rodrigo Blomqvist, Sylvie Breton, and Sven Enerbäck. 2009. The Forkhead Transcription Factor Foxi1 Is a Master Regulator of Vacuolar H+-ATPase Proton Pump Subunits in the Inner Ear, Kidney and Epididymis. PLoS ONE 4(2): e4471. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5335442
dc.description.abstract The vacuolar H\(^+\)-ATPase dependent transport of protons across cytoplasmic membranes in FORE (forkhead related) cells of endolymphatic epithelium in the inner ear, intercalated cells of collecting ducts in the kidney and in narrow and clear cells of epididymis require expression of several subunits that assemble into a functional multimeric proton pump. We demonstrate that expression of four such subunits A1, B1, E2 and a4 all co-localize with the forkhead transcription factor Foxi1 in a subset of epithelial cells at these three locations. In cells, of such epithelia, that lack Foxi1 we fail to identify any expression of A1, B1, E2 and a4 demonstrating an important role for the transcription factor Foxi1 in regulating subunit availability. Promoter reporter experiments, electrophoretic mobility shift assays (EMSA) and site directed mutagenesis demonstrate that a Foxi1 expression vector can trans-activate an a4-promoter reporter construct in a dose dependent manner. Furthermore, we demonstrate using chromatin immunoprecipitation (ChIP) assays that Foxi1-dependent activation to a large extent depends on cis-elements at position −561/−547 in the a4 promoter. Thus, we provide evidence that Foxi1 is necessary for expression of at least four subunits in three different epithelia and most likely is a major determinant for proper assembly of a functional vacuolar H\(^+\)-ATPase complex at these locations. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi://10.1371/journal.pone.0004471 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637605/pdf/ en_US
dash.license LAA
dc.subject biochemistry en_US
dc.subject cell biology en_US
dc.subject gene expression en_US
dc.subject non-clinical medicine en_US
dc.subject academic medicine en_US
dc.title The Forkhead Transcription Factor Foxi1 Is a Master Regulator of Vacuolar H\(^+\)-ATPase Proton Pump Subunits in the Inner Ear, Kidney and Epididymis en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Breton, Sylvie
dc.date.available 2011-11-01T14:59:34Z
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US

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