Objectif Retrotransposons (RTNs) are ancient viruses that have stably integrated themselves into mammalian genomes and they now occupy around half of the human or mouse genome. These mobile genetic elements that have coevolved with us drive evolution by creating new genes and plasticity of genomes. Exciting data including ours has shown that even RTNs that are no longer active retain enhancer, promoter or repressor sequences that regulate developmental genes, through largely uncharacterized transcription factors. We have employed CRISPR/Cas9 gene disruption to determine that Zfp37 and Zfp819 bind to and regulate RTNs in mouse embryonic stem cells (ESCs). Identification of these zinc finger proteins (ZFPs) now allows us to ask new questions about how RTNs have been co-opted to orchestrate gene circuits in vitro and in vivo. Both these factors have already been implicated to play a role in reprogramming or genome integrity. We hypothesize that RTNs have been co-opted to remodel the genome by acting as structural platforms that recruit transcription factors like Zfp37 and Zfp819. We will test this hypothesis assessing the role of RTNs and these two ZFPs in three dynamic contexts where the genome is remodelled. These are in ESC differentiation to neurons, in reprogramming and in early mouse development, three scenarios where RTNs have been documented to become expressed and serve an unknown function.This work will exploit mouse development to unravel the mechanism of how RTNs remodel the genome. It will help us to understand how ZFPs can be engaged to reprogram cells and in stem-cell therapies, and will explain more broadly how RTNs, which dominate our genomes, control cell fate. Champ scientifique natural sciencesbiological sciencesmicrobiologyvirologynatural scienceschemical sciencesinorganic chemistrytransition metalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsgenomes Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-StG-2015 - ERC Starting Grant Appel à propositions ERC-2015-STG Voir d’autres projets de cet appel Régime de financement ERC-STG - Starting Grant Institution d’accueil QUEEN MARY UNIVERSITY OF LONDON Contribution nette de l'UE € 999 137,00 Adresse 327 MILE END ROAD E1 4NS London Royaume-Uni Voir sur la carte Région London Inner London — East Tower Hamlets 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 € 999 137,00 Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire QUEEN MARY UNIVERSITY OF LONDON Royaume-Uni Contribution nette de l'UE € 999 137,00 Adresse 327 MILE END ROAD E1 4NS London Voir sur la carte Région London Inner London — East Tower Hamlets 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 € 999 137,00 UNIVERSITY COLLEGE LONDON Royaume-Uni Contribution nette de l'UE € 499 918,00 Adresse GOWER STREET WC1E 6BT London Voir sur la carte Région London Inner London — West Camden and City of London 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 € 499 918,00