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Epigenome maintenance in response to DNA damage

Project description

Integrity of epigenetic modifications following DNA damage

The chemical modifications on DNA and histone proteins are collectively known as the epigenome and play a central role in gene expression regulation. However, it is unclear how epigenetic modifications change in response to DNA damage and how they contribute to the repair response. To fill this knowledge gap, scientists of the EU-funded REMIND project will analyse histone modifications and DNA methylation status at DNA stretches under repair in human cells that have been subjected to UVC damage. Combined with detailed characterisation of the molecular players that contribute to chromatin restoration, this information will help dissect the maintenance and inheritance of epigenome after DNA repair.


Cell viability and homeostasis rely on the stable maintenance of the epigenetic information conveyed by chromatin, which associates DNA and histone proteins in the cell nucleus and governs gene expression programs. Yet, epigenome integrity is challenged during all DNA transactions, including DNA damage repair. While much effort has been devoted to characterizing chromatin alterations in response to DNA damage and how they contribute to the repair response, our knowledge of this fundamental process is largely incomplete, and whether and how epigenetic features are re-established following a genotoxic stress challenge is still unexplored. Thus, a comprehensive framework of the mechanisms underlying the maintenance of epigenome integrity in response to DNA damage is lacking.
The present project aims to fill this important gap by profiling the epigenome of repair patches following UVC damage in human cells and by characterizing the molecular players contributing to chromatin restoration/plasticity. I propose an integrated approach that tackles this question at different levels of chromatin organization, from histone and DNA modifications up to higher-order chromatin folding.
Building on our unique expertise and through the development of powerful novel methodologies, combining cutting-edge imaging, proteomics and epigenomic technologies, we will elucidate mechanisms for (1) histone modification re-establishment and maintenance and (2) DNA methylation inheritance at repair sites. We will also investigate how repair-associated changes in DNA and histone modifications reflect at the level of (3) higher-order chromatin organization in the tridimensional nuclear space, and dissect (4) functional crosstalks between the epigenetic changes that arise in damaged chromatin. This ambitious research project represents an unprecedented effort towards a comprehensive and integrated understanding of epigenome maintenance mechanisms in response to genotoxic stress.

Host institution

Net EU contribution
€ 1 446 250,00
75794 Paris

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Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Total cost
€ 1 738 750,00

Beneficiaries (2)