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.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.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.doi http://dx.doi.org/10.1126/sciadv.1701143
  • dc.identifier.issn 2375-2548
  • dc.identifier.uri http://hdl.handle.net/10230/59140
  • 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.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 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.accessRights info:eu-repo/semantics/openAccess
  • 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.type.version info:eu-repo/semantics/publishedVersion

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