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dc.contributor.author | Ortiz-Barahona, Amaya | - |
dc.contributor.author | Villar, Diego | - |
dc.contributor.author | Pescador, Nuria | - |
dc.contributor.author | Amigo, Jorge | - |
dc.contributor.author | Peso, Luis del | - |
dc.date.accessioned | 2013-05-28T11:23:42Z | - |
dc.date.available | 2013-05-28T11:23:42Z | - |
dc.date.issued | 2010 | - |
dc.identifier | doi: 10.1093/nar/gkp1205 | - |
dc.identifier | issn: 0305-1048 | - |
dc.identifier | e-issn: 1362-4962 | - |
dc.identifier.citation | Nucleic Acids Research 38(7): 2332-2345 (2010) | - |
dc.identifier.uri | http://hdl.handle.net/10261/76961 | - |
dc.description.abstract | The transcriptional response driven by Hypoxia-inducible factor (HIF) is central to the adaptation to oxygen restriction. Hence, the complete identification of HIF targets is essential for understanding the cellular responses to hypoxia. Herein we describe a computational strategy based on the combination of phylogenetic footprinting and transcription profiling meta-analysis for the identification of HIF-target genes. Comparison of the resulting candidates with published HIF1a genome-wide chromatin immunoprecipitation indicates a high sensitivity (78%) and specificity (97.8%). To validate our strategy, we performed HIF1a chromatin immunoprecipitation on a set of putative targets. Our results confirm the robustness of the computational strategy in predicting HIF-binding sites and reveal several novel HIF targets, including RE1-silencing transcription factor co-repressor (RCOR2). In addition, mapping of described polymorphisms to the predicted HIF-binding sites identified several single-nucleotide polymorphisms (SNPs) that could alter HIF binding. As a proof of principle, we demonstrate that SNP rs17004038, mapping to a functional hypoxia response element in the macrophage migration inhibitory factor (MIF) locus, prevents induction of this gene by hypoxia. Altogether, our results show that the proposed strategy is a powerful tool for the identification of HIF direct targets that expands our knowledge of the cellular adaptation to hypoxia and provides cues on the inter-individual variation in this response. | - |
dc.description.sponsorship | Ministerio de Ciencia y Tecnología/Ministerio de Ciencia e Innovación (SAF2005-00180 and SAF2008-03147), Comunidad Autónoma de Madrid (S-SAL-0311_2006); and the METOXIA, project ref. HEALTH-F2-2009-222741, under the 7th Research Framework Programme of the European Union. Funding for open access charge: SAF2008-03147. | - |
dc.language.iso | eng | - |
dc.publisher | Oxford University Press | - |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/222741 | - |
dc.rights | openAccess | - |
dc.title | Genome-wide identification of hypoxia-inducible factor binding sites and target genes by a probabilistic model integrating transcription-profiling data and in silico binding site prediction | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1093/nar/gkp1205 | - |
dc.relation.publisherversion | http://dx.doi.org/10.1093/nar/gkp1205 | - |
dc.date.updated | 2013-05-28T11:23:42Z | - |
dc.description.version | Peer Reviewed | - |
dc.identifier.pmid | 20061373 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.languageiso639-1 | en | - |
item.fulltext | With Fulltext | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
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