Objective 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. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesmathematicsapplied mathematicsmathematical model Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-COG - ERC Consolidator Grant Call for proposal ERC-2016-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA Net EU contribution € 335 492,00 Address Am Campus 1 3400 Klosterneuburg Austria See on map Region Ostösterreich Niederösterreich Wiener Umland/Nordteil Activity type Higher or Secondary Education Establishments 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 € 335 492,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA Austria Net EU contribution € 335 492,00 Address Am Campus 1 3400 Klosterneuburg See on map Region Ostösterreich Niederösterreich Wiener Umland/Nordteil Activity type Higher or Secondary Education Establishments 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 € 335 492,00 JOHN INNES CENTRE United Kingdom Net EU contribution € 2 414 470,00 Address NORWICH RESEARCH PARK COLNEY NR4 7UH Norwich See on map Region East of England East Anglia Breckland and South Norfolk 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 € 2 414 470,00