Project description DEENESFRITPL Research could uncover how polycomb-group proteins promote epigenetic switching The epigenetic regulation of gene expression through polycomb-group proteins is central to the development and environmental plasticity of most eukaryotes. A class of polycomb-group proteins, PRC2 can epigenetically silence genomic sites known as nucleation regions or polycomb response elements. The EU-funded EPISWITCH project will use a well-characterised gene system, Arabidopsis FLC, to elucidate the core epigenetic switching mechanisms that this family of protein complexes puts into place. This interdisciplinary project will determine the local chromatin features that promote the epigenetic switch independently at each allele. It will also describe how DNA replication affects the transition from metastable to long-term epigenetic silencing. Show the project objective Hide the project objective Objective Polycomb-mediated epigenetic regulation of gene expression is central to development and environmental plasticity in most eukaryotes. Polycomb Repressive Complex 2 (PRC2) is targeted to genomic sites, known as nucleation regions or Polycomb Response elements, and switches those targets to an epigenetically silenced state. But what constitutes the switching mechanism is unknown. Core epigenetic switching mechanisms have proven difficult to elucidate due to the complex molecular feedbacks involved. We will exploit a well-characterized gene system, Arabidopsis FLC, to address a central question – what are the core events that constitute a Polycomb switch? Our hypothesis is that the epigenetic switch involves stochastic conformationally-induced oligomerization, generating an ordered protein assembly of PRC2 accessory proteins and PRC2, that is then robustly distributed onto both daughter strands during DNA replication through self-templating feedback mechanisms. We will determine the local chromatin features that promote the epigenetic switch independently at each allele (i.e. in cis). We will also dissect the involvement of DNA replication in the transition from metastable to long-term epigenetic silencing, associated with the Polycomb complex spreading across the body of the locus. This interdisciplinary proposal combines molecular genetics/biology, computational biology, with structural biology, achieved through close working relationships with Prof. Martin Howard (John Innes Centre), Dr Mariann Bienz (MRC Laboratory of Molecular Biology, Cambridge) and Dr Julian Sale, (MRC Laboratory of Molecular Biology, Cambridge). This blue-sky programme aims to provide important new concepts in Polycomb-mediated epigenetic switching mechanisms, important for the whole epigenetics field. Fields of science natural sciencesbiological sciencesmolecular biologymolecular geneticsnatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsepigeneticsnatural sciencesbiological sciencesmolecular biologystructural biology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-ADG - ERC Advanced Grant Call for proposal ERC-2018-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Coordinator JOHN INNES CENTRE Net EU contribution € 2 101 325,00 Address Norwich research park colney NR4 7UH Norwich GB 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 Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all JOHN INNES CENTRE GB Net EU contribution € 2 101 325,00 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 Other funding € 0,00
