Objectif Cytosine methylation is a chemical modification that is precisely copied when DNA is replicated. Because methylation can regulate gene expression, accurate reproduction of DNA methylation patterns is essential for plant and animal development and for human health. The enzymes that maintain DNA methylation have to work within chromatin, and particularly to contend with nucleosomes – tight complexes of DNA and histone proteins. How methylation of nucleosomal DNA is maintained remains unknown, and even the simple matter of whether nucleosomes hinder or promote methylation is controversial.My laboratory’s recent work with DDM1 – an ancient protein conserved between plants and animals that can move nucleosomes – and linker histone H1, which binds to nucleosomes and the intervening ‘linker’ DNA, has allowed us to formulate a model wherein movement of nucleosomes by DDM1 dislodges H1 and allows methyltransferases to access the DNA. Furthermore, this work revealed the existence of unknown factors required to maintain DNA methylation. My laboratory also discovered that DNA methylation influences nucleosome placement, thereby demonstrating that the interaction between DNA methylation and nucleosomes is bidirectional.My goal is now to deeply understand the connected processes of maintenance methylation and nucleosome placement. This will be achieved through three interconnected research strands:1) Elucidation of how DNA methylation is maintained within chromatin.2) Identification of new DNA methylation maintenance factors.3) Determination of how DNA methylation influences nucleosomes in vivo.Our ultimate output will be the creation of a mathematical model of DNA methylation maintenance that will incorporate the bidirectional interactions between methylation and nucleosomes. This breakthrough will revolutionize research in the field by permitting the development of precise, quantitative hypotheses about the maintenance and function of DNA methylation within chromatin. Champ scientifique natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesmathematicsapplied mathematicsmathematical model Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2016-COG - ERC Consolidator Grant Appel à propositions ERC-2016-COG Voir d’autres projets de cet appel Régime de financement ERC-COG - Consolidator Grant Institution d’accueil INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA Contribution nette de l'UE € 335 492,00 Adresse Am Campus 1 3400 Klosterneuburg Autriche Voir sur la carte Région Ostösterreich Niederösterreich Wiener Umland/Nordteil Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 335 492,00 Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA Autriche Contribution nette de l'UE € 335 492,00 Adresse Am Campus 1 3400 Klosterneuburg Voir sur la carte Région Ostösterreich Niederösterreich Wiener Umland/Nordteil Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 335 492,00 JOHN INNES CENTRE Royaume-Uni Contribution nette de l'UE € 2 414 470,00 Adresse NORWICH RESEARCH PARK COLNEY NR4 7UH Norwich Voir sur la carte Région East of England East Anglia Breckland and South Norfolk Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 414 470,00
