Unravelling the hidden DNA structural/physical code provides novel insights on promoter location

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• dc.contributor.author Durán, Elisaca
• dc.contributor.author Djebali, Sarahca
• dc.contributor.author González, Santica
• dc.contributor.author Flores, Oscarca
• dc.contributor.author Mercader Bigas, Josep Mariaca
• dc.contributor.author Guigó Serra, Rodericca
• dc.contributor.author Torrents, Davidca
• dc.contributor.author Soler López, Montserratca
• dc.contributor.author Orozco, Modestoca
• dc.date.accessioned 2015-02-06T08:10:11Z
• dc.date.available 2015-02-06T08:10:11Z
• dc.date.issued 2013ca
• dc.description.abstract Although protein recognition of DNA motifs in promoter regions has been traditionally considered as a critical regulatory element in transcription, the location of promoters, and in particular transcription start sites (TSSs), still remains a challenge. Here we perform a comprehensive analysis of putative core promoter sequences relative to non-annotated predicted TSSs along the human genome, which were defined by distinct DNA physical properties implemented in our ProStar computational algorithm. A representative sampling of predicted regions was subjected to extensive experimental validation and analyses. Interestingly, the vast majority proved to be transcriptionally active despite the lack of specific sequence motifs, indicating that physical signaling is indeed able to detect promoter activity beyond conventional TSS prediction methods. Furthermore, highly active regions displayed typical chromatin features associated to promoters of housekeeping genes. Our results enable to redefine the promoter signatures and analyze the diversity, evolutionary conservation and dynamic regulation of human core promoters at large-scale. Moreover, the present study strongly supports the hypothesis of an ancient regulatory mechanism encoded by the intrinsic physical properties of the DNA that may contribute to the complexity of transcription regulation in the human genome.
• dc.description.sponsorship This work was supported by the Spanish Ministry of Science and Innovation [BIO2012-32868 and Consolider E-Science Project]; Instituto de Salud Carlos III (Instituto Nacional de Bioinformática);/nEuropean Research Council (ERC) Advanced Grant; Fundación Marcelino Botín. M.O. is an Institució Catalana de Recerca i Estudis Avançats (ICREA) Academia Researcher. Funding for open access charge: Fundación Marcelino Botín
• dc.format.mimetype application/pdfca
• dc.identifier.citation Durán E, Djebali S, González S, Flores O, Mercader JM, Guigó R et al. Unravelling the hidden DNA structural/physical code provides novel insights on promoter location. Nucleic Acids Res. 2013;41(15):7220-30. DOI: 10.1093/nar/gkt511ca
• dc.identifier.doi http://dx.doi.org/10.1093/nar/gkt511
• dc.identifier.issn 0305-1048ca
• dc.identifier.uri http://hdl.handle.net/10230/23104
• dc.language.iso engca
• dc.publisher Oxford University Pressca
• dc.relation.ispartof Nucleic Acids Research. 2013;41(15):7220-30
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2012-32868
• dc.rights © 2013 Elisa Durán et al. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution License which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly citedca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/3.0/
• dc.subject.other Genoma humà
• dc.subject.other Genètica
• dc.title Unravelling the hidden DNA structural/physical code provides novel insights on promoter locationca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca