EPISWITCH
Financiado
Mechanistic basis of nucleation and spreading underlying a Polycomb mediated epi...
Mechanistic basis of nucleation and spreading underlying a Polycomb mediated epigenetic switch
Polycomb-mediated epigenetic regulation of gene expression is central to development and environmental plasticity in most eukaryotes. Polycomb Repressive Complex 2 (PRC2) is targeted to genomic sites, known as nucleation regions o...
Polycomb-mediated epigenetic regulation of gene expression is central to development and environmental plasticity in most eukaryotes. Polycomb Repressive Complex 2 (PRC2) is targeted to genomic sites, known as nucleation regions or Polycomb Response elements, and switches those targets to an epigenetically silenced state. But what constitutes the switching mechanism is unknown. Core epigenetic switching mechanisms have proven difficult to elucidate due to the complex molecular feedbacks involved. We will exploit a well-characterized gene system, Arabidopsis FLC, to address a central question – what are the core events that constitute a Polycomb switch?
Our hypothesis is that the epigenetic switch involves stochastic conformationally-induced oligomerization, generating an ordered protein assembly of PRC2 accessory proteins and PRC2, that is then robustly distributed onto both daughter strands during DNA replication through self-templating feedback mechanisms. We will determine the local chromatin features that promote the epigenetic switch independently at each allele (i.e., in cis). We will also dissect the involvement of DNA replication in the transition from metastable to long-term epigenetic silencing, associated with the Polycomb complex spreading across the body of the locus.
This interdisciplinary proposal combines molecular genetics/biology, computational biology, with structural biology, achieved through close working relationships with Prof. Martin Howard (John Innes Centre), Dr Mariann Bienz (MRC Laboratory of Molecular Biology, Cambridge) and Dr Julian Sale, (MRC Laboratory of Molecular Biology, Cambridge). This blue-sky programme aims to provide important new concepts in Polycomb-mediated epigenetic switching mechanisms, important for the whole epigenetics field.
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Duración del proyecto: 76 meses
Fecha Inicio: 2019-04-17
Fecha Fin: 2025-08-31
Fecha Fin: 2025-08-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2019-04-17
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2018-ADG:
ERC Advanced Grant
Cerrada
hace 6 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
JOHN INNES CENTRE
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
1.35M€ |
Participante