Objective A central question in chromatin biology is how to organize the genome and mark specific regions with histone variants. Understanding how to establish and maintain, but also change chromatin states is a fundamental challenge. Histone chaperones, escort factors that regulate the supply, loading, and degradation of histone variants, are key in their placement at specific chromatin landmarks and bridge organization from nucleosomes to higher order structures. A series of studies have underlined chaperone-variant partner selectivity in multicellular organisms, yet recently, dosage imbalances in natural and pathological contexts highlight plasticity in these interactions. Considering known changes in histone dosage during development, one should evaluate chaperone function not as fixed modules, but as a dynamic circuitry that adapts to cellular needs during the cell cycle, replication and repair, differentiation, development and pathology.Here we propose to decipher the mechanisms enabling adaptability to natural and experimentally induced changes in the dosage of histone chaperones and variants over time. To follow new and old proteins, and control dosage, we will engineer cellular and animal models and exploit quantitative readout methods using mass spectrometry, imaging, and single-cell approaches. We will evaluate with an unprecedented level of detail the impact on i) soluble histone complexes and ii) specific chromatin landmarks (centromere, telomeres, heterochromatin and regulatory elements) and their crosstalk. We will apply this to determine the impact of these parameters during distinct developmental transitions, such as ES cell differentiation and T cell commitment in mice. We aim to define general principles for variants in nuclear organization and dynamic changes during the cell cycle/repair and in differentiation and unravel locus specific-roles of chaperones as architects and bricklayers of the genome, in designing and building specific nuclear domains. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopynatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomes Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-ADG-2015 - ERC Advanced Grant Call for proposal ERC-2015-AdG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution INSTITUT CURIE Net EU contribution € 1 985 660,94 Address RUE D ULM 26 75231 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 € 2 499 697,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all INSTITUT CURIE France Net EU contribution € 1 985 660,94 Address RUE D ULM 26 75231 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 € 2 499 697,00 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. CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS France Net EU contribution € 514 036,06 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 € 514 036,06
