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dc.contributor.authorAlotaibi, H.en_US
dc.contributor.authorYaman, E.en_US
dc.contributor.authorSalvatore, D.en_US
dc.contributor.authordi Dato, V.en_US
dc.contributor.authorTelkoparan, P.en_US
dc.contributor.authordi Lauro, R.en_US
dc.contributor.authorTazebay, U. H.en_US
dc.date.accessioned2016-02-08T10:00:18Z
dc.date.available2016-02-08T10:00:18Z
dc.date.issued2010en_US
dc.identifier.issn0305-1048
dc.identifier.urihttp://hdl.handle.net/11693/22454
dc.description.abstractActivity of the sodium/iodide symporter (NIS) in lactating breast is essential for iodide (I-) accumulation in milk. Significant NIS upregulation was also reported in breast cancer, indicating a potential use of radioiodide treatment. All-trans-retinoic acid (tRA) is a potent ligand that enhances NIS expression in a subset of breast cancer cell lines and in experimental breast cancer models. Indirect tRA stimulation of NIS in breast cancer cells is very well documented; however, direct upregulation by tRA-activated nuclear receptors has not been identified yet. Aiming to uncover cis-acting elements directly regulating NIS expression, we screened evolutionary-conserved non-coding genomic sequences for responsiveness to tRA in MCF-7. Here, we report that a potent enhancer in the first intron of NIS mediates direct regulation by tRA-stimulated nuclear receptors. In vitro as well as in vivo DNA-protein interaction assays revealed direct association between retinoic acid receptor-α (RARα) and retinoid-X-receptor (RXR) with this enhancer. Moreover, using chromatin immunoprecipitation (ChIP) we uncovered early events of NIS transcription in response to tRA, which require the interaction of several novel intronic tRA responsive elements. These findings indicate a complex interplay between nuclear receptors, RNA Pol-II and multiple intronic RAREs in NIS gene, and they establish a novel mechanistic model for tRA-induced gene transcription. © The Author(s) 2010. Published by Oxford University Press.en_US
dc.language.isoEnglishen_US
dc.source.titleNucleic Acids Researchen_US
dc.relation.isversionofhttp://dx.doi.org/10.1093/nar/gkq023en_US
dc.subjectCell nucleus receptoren_US
dc.subjectRetinoic aciden_US
dc.subjectRetinoic acid receptoren_US
dc.subjectRetinoic acid receptor alphaen_US
dc.subjectRetinoid X receptoren_US
dc.subjectRNA polymerase IIen_US
dc.subjectSodium iodide symporteren_US
dc.titleIntronic elements in the Na+/I-symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcriptionen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.citation.spage3172en_US
dc.citation.epage3185en_US
dc.citation.volumeNumber38en_US
dc.citation.issueNumber10en_US
dc.identifier.doi10.1093/nar/gkq023en_US
dc.publisherOxford University Pressen_US


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