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Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory

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dc.contributor.author Klosin, Adam
dc.contributor.author Reis, Kadri, 1985-
dc.contributor.author Hidalgo-Carcedo, Cristina
dc.contributor.author Casas, Eduard
dc.contributor.author Vavouri, Tanya
dc.contributor.author Lehner, Ben, 1978-
dc.date.accessioned 2024-02-19T10:08:19Z
dc.date.available 2024-02-19T10:08:19Z
dc.date.issued 2017
dc.identifier.citation Klosin A, Reis K, Hidalgo-Carcedo C, Casas E, Vavouri T, Lehner B. Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory. Sci Adv. 2017 Aug;3(8):e1701143. DOI: 10.1126/sciadv.1701143
dc.identifier.issn 2375-2548
dc.identifier.uri http://hdl.handle.net/10230/59140
dc.description Includes supplementary materials.
dc.description.abstract Impaired DNA replication is a hallmark of cancer and a cause of genomic instability. We report that, in addition to causing genetic change, impaired DNA replication during embryonic development can have major epigenetic consequences for a genome. In a genome-wide screen, we identified impaired DNA replication as a cause of increased expression from a repressed transgene in Caenorhabditis elegans. The acquired expression state behaved as an “epiallele,” being inherited for multiple generations before fully resetting. Derepression was not restricted to the transgene but was caused by a global reduction in heterochromatin-associated histone modifications due to the impaired retention of modified histones on DNA during replication in the early embryo. Impaired DNA replication during development can therefore globally derepress chromatin, creating new intergenerationally inherited epigenetic expression states.
dc.description.sponsorship This work was supported by a European Research Council Consolidator grant (616434), the Spanish Ministry of Economy and Competitiveness (BFU2011-26206 and “Centro de Excelencia Severo Ochoa 2013-2017” SEV-2012-0208), the AXA Research Fund, the Bettencourt-Schueller Foundation, Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR), FP7 project 4DCellFate (277899), and the European Molecular Biology Laboratory–CRG Systems Biology Program. A.K. was partially supported by a la Caixa Fellowship. E.C. and T.V. are supported by the Spanish Ministry of Economy and Competitiveness (grants BFU2015-70581 and IEDI-2016-00787). E.C. is supported by an FI AGAUR PhD fellowship.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher American Association for the Advancement of Science (AAAS)
dc.relation.ispartof Science Advances. 2017 Aug;3(8):e1701143
dc.rights Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.subject.other ADN
dc.subject.other Genomes
dc.subject.other Embriologia
dc.title Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1126/sciadv.1701143
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/277899
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-26206
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SEV-2012-0208
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-70581
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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