4D Genome rewiring during oncogene-induced and replicative senescende

To understand the role of the extensive senescence-associated 3D genome reorganization, we generated genome-wide chromatin interaction maps, epigenome, replication-timing, whole-genome bisulfite sequencing, and gene expression profiles from cells entering replicative senescence (RS) or upon oncogene...

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Detalles Bibliográficos
Autores: Sati, Satish, Bonev, Boyan, Szabo, Quentin, Jost, Daniel, Bensadoun, Paul, Serra, Francois, Loubiere, Vincent, Papadopoulos, Giorgio Lucio, Rivera-Mulia, Juan-Carlos, Frisch, Lauriane, Bouret, Pauline, Castillo, David, Gelpí Buchaca, Josep Lluís, Orozco López, Modesto, Vaillant, Cedric, Pellestor, Franck, Bantignies, Frederic, Martí Renom, Marc A., Gilbert, David M., Lemaitre, Jean-Marc, Cavalli, Giacomo
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/172030
Acceso en línea:https://hdl.handle.net/2445/172030
Access Level:acceso abierto
Palabra clave:Oncogènesi
Cromatina
Epigenètica
Carcinogenesis
Chromatin
Epigenetics
Descripción
Sumario:To understand the role of the extensive senescence-associated 3D genome reorganization, we generated genome-wide chromatin interaction maps, epigenome, replication-timing, whole-genome bisulfite sequencing, and gene expression profiles from cells entering replicative senescence (RS) or upon oncogene-induced senescence (OIS). We identify senescence-associated heterochromatin domains (SAHDs). Differential intra- versus inter-SAHD interactions lead to the formation of senescence-associated heterochromatin foci (SAHFs) in OIS but not in RS. This OIS-specific configuration brings active genes located in genomic regions adjacent to SAHDs in close spatial proximity and favors their expression.We also identify DNMT1 as a factor that induces SAHFs by promoting HMGA2 expression. Upon DNMT1 depletion, OIS cells transition to a 3D genome conformation akin to that of cells in replicative senescence. These data show how multi-omics and imaging can identify critical features of RS and OIS and discover determinants of acute senescence and SAHF formation.

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