Objetivo A PubMed search for ‘epigenetic’ identifies nearly 35,000 entries, yet the molecular mechanisms by which chromatin modification and gene expression patterns are actually inherited during chromosome replication — mechanisms which lie at the heart of epigenetic inheritance of gene expression — are still largely uncharacterised. Understanding these mechanisms would be greatly aided if we could reconstitute the replication of chromosomes with purified proteins. The past few years have seen great progress in understanding eukaryotic DNA replication through the use of cell-free replication systems and reconstitution of individual steps in replication with purified proteins and naked DNA. We will use these in vitro replication systems together with both established and novel chromatin assembly systems to understand: a) how chromatin influences replication origin choice and timing, b) how nucleosomes on parental chromosomes are disrupted during replication and are distributed to daughter chromatids, and c) how chromatin states and gene expression patterns are re-established after passage of the replication fork. We will begin with simple, defined templates to learn basic principles, and we will use this knowledge to reconstitute genome-wide replication patterns. The experimental plan will exploit our well-characterised yeast systems, and where feasible explore these questions with human proteins. Our work will help explain how epigenetic inheritance works at a molecular level, and will complement work in vivo by many others. It will also underpin our long-term research goals aimed at making functional chromosomes from purified, defined components to understand how DNA replication interacts with gene expression, DNA repair and chromosome segregation. Ámbito científico natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Palabras clave CHROMOREP Programa(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Tema(s) ERC-ADG-2014 - ERC Advanced Grant Convocatoria de propuestas ERC-2014-ADG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-ADG - Advanced Grant Institución de acogida THE FRANCIS CRICK INSTITUTE LIMITED Aportación neta de la UEn € 1 983 019,00 Dirección 1 MIDLAND ROAD NW1 1AT London Reino Unido Ver en el mapa Región London Inner London — West Camden and City of London Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 983 019,00 Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo THE FRANCIS CRICK INSTITUTE LIMITED Reino Unido Aportación neta de la UEn € 1 983 019,00 Dirección 1 MIDLAND ROAD NW1 1AT London Ver en el mapa Región London Inner London — West Camden and City of London Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 983 019,00