Project description DEENESFRITPL Histones and DNA replication Epigenetic phenomena play a role in cellular differentiation during development, cancer development and disease susceptibility. While the inheritance of chromatin components is accepted as a driving force behind these phenomena, the role of histones and their inheritance pattern have not been fully elucidated. Funded by the European Research Council, the NChIP project will investigate how histones and chromatin regulators move during DNA replication in yeast. The idea is to determine how chromatin states withstand the disturbances caused by DNA replication. Results will contribute significantly to the understanding of the process of chromatin assembly and its role in maintaining the integrity of genetic information. Show the project objective Hide the project objective Objective Chromatin assembly is a fundamental cellular process necessary for the maintenance of genome integrity and transcriptional programs. Understanding the effect of DNA replication on histone protein dynamics is also a prerequisite for understanding the role of chromatin in epigenetic inheritance. Epigenetic phenomena are thought to influence cellular differentiation and cancer formation, as well as the impact of environmental factors on early development and later predispositions to disease. While epigenetic inheritance of chromatin components is, in theory, accepted as the driver of such phenomena, chromatin state inheritance per se has only been demonstrated for a few specific cases. Not much is known about histone “inheritance” beyond the facts that bulk maternal histones distribute equally among the daughter strands and are diluted two-fold after replication with newly synthesized “unmarked” histones, and that the majority of H3/H4 tetramers do not split before reassembly. We have shown previously that maternal nucleosomes stay on average within 400bp of their original binding site, implying that any potentially heritable chromatin encoded information, has to be inherited in ~1kb blocs, as smaller nucleosome domains would rapidly be diluted by new nucleosomes. I propose to develop high throughput systems for directly measuring movements of histones and chromatin regulators during genomic replication in S.cerevisiae to determine, how chromatin states survive the perturbations associated with replication. We will determine locus specific differences in the spread of maternal nucleosomes after replication, the effects of leading and lagging strand replication on nucleosome positioning and maternal nucleosome distribution, the renewal dynamics of posttranslational histone marks and chromatin binding proteins, and the kinetics of chromatin footprint re-establishment and gene (re)activation. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2014 - ERC Consolidator Grant Call for proposal ERC-2014-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Net EU contribution € 1 984 677,00 Address RUE MICHEL ANGE 3 75794 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 984 677,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS France Net EU contribution € 1 984 677,00 Address RUE MICHEL ANGE 3 75794 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 984 677,00
