Project description DEENESFRITPL Integrity of epigenetic modifications following DNA damage The chemical modifications on DNA and histone proteins are collectively known as the epigenome and play a central role in gene expression regulation. However, it is unclear how epigenetic modifications change in response to DNA damage and how they contribute to the repair response. To fill this knowledge gap, scientists of the EU-funded REMIND project will analyse histone modifications and DNA methylation status at DNA stretches under repair in human cells that have been subjected to UVC damage. Combined with detailed characterisation of the molecular players that contribute to chromatin restoration, this information will help dissect the maintenance and inheritance of epigenome after DNA repair. Show the project objective Hide the project objective Objective Cell viability and homeostasis rely on the stable maintenance of the epigenetic information conveyed by chromatin, which associates DNA and histone proteins in the cell nucleus and governs gene expression programs. Yet, epigenome integrity is challenged during all DNA transactions, including DNA damage repair. While much effort has been devoted to characterizing chromatin alterations in response to DNA damage and how they contribute to the repair response, our knowledge of this fundamental process is largely incomplete, and whether and how epigenetic features are re-established following a genotoxic stress challenge is still unexplored. Thus, a comprehensive framework of the mechanisms underlying the maintenance of epigenome integrity in response to DNA damage is lacking. The present project aims to fill this important gap by profiling the epigenome of repair patches following UVC damage in human cells and by characterizing the molecular players contributing to chromatin restoration/plasticity. I propose an integrated approach that tackles this question at different levels of chromatin organization, from histone and DNA modifications up to higher-order chromatin folding. Building on our unique expertise and through the development of powerful novel methodologies, combining cutting-edge imaging, proteomics and epigenomic technologies, we will elucidate mechanisms for (1) histone modification re-establishment and maintenance and (2) DNA methylation inheritance at repair sites. We will also investigate how repair-associated changes in DNA and histone modifications reflect at the level of (3) higher-order chromatin organization in the tridimensional nuclear space, and dissect (4) functional crosstalks between the epigenetic changes that arise in damaged chromatin. This ambitious research project represents an unprecedented effort towards a comprehensive and integrated understanding of epigenome maintenance mechanisms in response to genotoxic stress. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesgeneticsepigenetics Keywords DNA damage repair Epigenome integrity Histone modifications DNA methylation Higher-order chromatin organization Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-COG - ERC Consolidator Grant Call for proposal ERC-2018-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 € 1 446 250,00 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 € 1 738 750,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS France Net EU contribution € 1 446 250,00 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 € 1 738 750,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France Net EU contribution € 292 500,00 Address RUE DE TOLBIAC 101 75654 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 € 292 500,00
