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


Por: Klosin, A, Reis, K, Hidalgo-Carcedo, C, Casas, E, Vavouri, T and Lehner, B
Publicada: 1 ago 2017
Categoría: Multidisciplinary
Resumen:
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.
Filiaciones:
Klosin, A:
 Barcelona Inst Sci & Technol, CRG, Ctr Genom Regulat EMBL CRG, European Mol Biol Lab,Syst Biol Unit, Barcelona 08003, Spain

 Univ Pompeu Fabra, Barcelona 08003, Spain
Reis, K:
 Barcelona Inst Sci & Technol, CRG, Ctr Genom Regulat EMBL CRG, European Mol Biol Lab,Syst Biol Unit, Barcelona 08003, Spain

 Univ Pompeu Fabra, Barcelona 08003, Spain
Hidalgo-Carcedo, C:
 Barcelona Inst Sci & Technol, CRG, Ctr Genom Regulat EMBL CRG, European Mol Biol Lab,Syst Biol Unit, Barcelona 08003, Spain

 Univ Pompeu Fabra, Barcelona 08003, Spain
Casas, E:
 Inst Germans Trias & Pujol, Program Predict & Personalized Med Canc, Can Ruti Campus,Ctra Can Ruti,Cami Escoles S-N, Barcelona 08916, Spain
:
 Inst Germans Trias & Pujol, Program Predict & Personalized Med Canc, Can Ruti Campus,Ctra Can Ruti,Cami Escoles S-N, Barcelona 08916, Spain

 Josep Carreras Leukaemia Res Inst IJC, Can Ruti Campus,Ctra Can Ruti,Cami Escoles S-N, Barcelona 08916, Spain
Lehner, B:
 Barcelona Inst Sci & Technol, CRG, Ctr Genom Regulat EMBL CRG, European Mol Biol Lab,Syst Biol Unit, Barcelona 08003, Spain

 Univ Pompeu Fabra, Barcelona 08003, Spain

 Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Spain
ISSN: 23752548





Science Advances
Editorial
American Association for the Advancement of Science, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 3 Número: 8
Páginas:
WOS Id: 000411589900040
ID de PubMed: 28835928
imagen Green Published, gold

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