XICUT
Financiado
Epigenome establishment and maintenance of the inactive X chromosome in response...
Epigenome establishment and maintenance of the inactive X chromosome in response to DNA double-strand breaks in mammalian cells
The DNA damage response takes place on a chromatin substrate and triggers profound chromatin alterations. Chromatin states vary substantially between genomic regions, driving distinct gene expression profiles and also different DN...
The DNA damage response takes place on a chromatin substrate and triggers profound chromatin alterations. Chromatin states vary substantially between genomic regions, driving distinct gene expression profiles and also different DNA damage repair responses. One striking example is the heterochromatinization of an entire chromosome, the inactive X chromosome in female mammals, that is silenced during embryonic development by facultative heterochromatin formation. How the facultative heterochromatin state of the inactive X responds to DNA damage and impacts DNA repair is poorly understood. My research project aims at identifying chromatin changes that accompany the repair of the most cytotoxic form of DNA damage, DNA double-strand breaks (DSBs), in facultative heterochromatin and the mechanisms that ensure the establishment and maintenance of the inactive X chromosome in response to DNA damage in mammalian cells. To generate DSBs, I use the CRISPR/Cas9 technology that allows sequence-specific targeting of the Cas9 nuclease. Thanks to available bioinformatic tools, I can discriminate between active and inactive X chromosomes, analyze the genomic instability profiles induced around the break sites and decipher the repair pathway involved. In parallel, I will profile the chromatin marks associated with the inactive X chromosome in the vicinity of DSBs to assess the impact of DNA damage and repair on heterochromatin maintenance. Moreover, I will test the hypothesis that the high level of replicative stress-induced breaks in embryonic stem cells could drive heterochromatin establishment and thus skew the choice of the inactive X chromosome. For this, I will study the impact of generating DSBs on one X chromosome of mouse stem cells on their differentiation potential and their propension to inactivate the damaged X chromosome. Together, this work should shed light on the interplay between the DSB response and facultative heterochromatin states.
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Duración del proyecto: 28 meses
Fecha Inicio: 2023-08-03
Fecha Fin: 2025-12-31
Fecha Fin: 2025-12-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-08-03
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2022-PF-01-01:
MSCA Postdoctoral Fellowships 2022
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
212K€
Líder del proyecto
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE...
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Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5