A role for insulator elements in the regulation of gene expression response to hypoxia

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dc.contributor.author Tiana, María
dc.contributor.author Villar Lozano, Diego
dc.contributor.author Pérez-Guijarro, Eva
dc.contributor.author Gómez-Maldonado, Laura
dc.contributor.author Moltó, Eduardo
dc.contributor.author Fernández-Miñán, Ana
dc.contributor.author Gómez-Skármeta, José Luis
dc.contributor.author Montoliu, Lluís
dc.contributor.author Del Peso, Luis
dc.contributor.other UAM. Departamento de Bioquímica es_ES
dc.date.accessioned 2015-04-08T08:09:41Z
dc.date.available 2015-04-08T08:09:41Z
dc.date.issued 2012-03-01
dc.identifier.citation Nucleic Acids Research 40.5 (2012): 1916-1927 en_US
dc.identifier.issn 0305-1048 (print) en_US
dc.identifier.issn 1362-4962 (online) en_US
dc.identifier.uri http://hdl.handle.net/10486/664888
dc.description.abstract Hypoxia inducible factor (HIF) up-regulates the transcription of a few hundred genes required for the adaptation to hypoxia. This restricted set of targets is in sharp contrast with the widespread distribution of the HIF binding motif throughout the genome. Here, we investigated the transcriptional response of GYS1 and RUVBL2 genes to hypoxia to understand the mechanisms that restrict HIF activity toward specific genes. GYS1 and RUVBL2 genes are encoded by opposite DNA strands and separated by a short intergenic region (∼1kb) that contains a functional hypoxia response element equidistant to both genes. However, hypoxia induced the expression of GYS1 gene only. Analysis of the transcriptional response of chimeric constructs derived from the intergenic region revealed an inhibitory sequence whose deletion allowed RUVBL2 induction by HIF. Enhancer blocking assays, performed in cell culture and transgenic zebrafish, confirmed the existence of an insulator element within this inhibitory region that could explain the differential regulation of GYS1 and RUVBL2 by hypoxia. Hence, in this model, the selective response to HIF is achieved with the aid of insulator elements. This is the first report suggesting a role for insulators in the regulation of differential gene expression in response to environmental signals en_US
dc.description.sponsorship The Ministerio de Ciencia e Innovación (Spanish Ministry of Science and Innovation, MICINN) grant numbers Nucleic Acids Research, 2012, Vol. 40, No. 5 1925 SAF2008-03147 (to L.del P.), BIO2009-1297 (to L.M.), BFU2010-14839 (to J.L.G.-S.), CSD2007-00008 (to J.L.G.-S.); Comunidad Autónoma de Madrid grant number S-SAL-0311_2006 (to L.del P.); the 7th Research Framework Programme of the European Union grant number METOXIA project ref. HEALTH-F2-2009-222741 (to L.del P.); Junta de Andalucía grant number CVI-3488 (to J.L.G.-S.); CIBERER (ISCIII) (to E.M.). Funding for open access charge: SAF2008-03147 (to L.del P.) en_US
dc.format.extent 12 pag. es_ES
dc.format.mimetype application/pdf es_ES
dc.language.iso eng es_ES
dc.publisher Oxford University Press en_US
dc.relation.ispartof Nucleic Acids Research en_US
dc.rights © 2011 The Author(s) en_US
dc.subject.other Carrier Proteins en_US
dc.subject.other DNA es_ES
dc.subject.other Gene Expression Regulation en_US
dc.subject.other Glycogen Synthase en_US
dc.subject.other Insulator Elements en_US
dc.title A role for insulator elements in the regulation of gene expression response to hypoxia en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.identifier.doi 10.1093/nar/gkr842 es_ES
dc.identifier.publicationfirstpage 1916 es_ES
dc.identifier.publicationissue 5 es_ES
dc.identifier.publicationlastpage 1927 es_ES
dc.identifier.publicationvolume 40 es_ES
dc.relation.projectID Comunidad de Madrid. S2006/SAL-0311 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/222741 en_US
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento – NoComercial es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Villar Lozano, Diego (263587)
dc.authorUAM Tiana Cerrolaza, María (264557)

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