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Chromatin Adaptations through Interactions of Chaperones in Time

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.

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Topic(s)

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2015-AdG

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Host institution

INSTITUT CURIE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 985 660,94
Address
RUE D ULM 26
75231 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 499 697,00

Beneficiaries (2)

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