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2020-05-07

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cc-by-nc-nd (c) Elsevier, 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/172030

4D Genome rewiring during oncogene-induced and replicative senescende

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https://doi.org/10.1016/j.molcel.2020.03.007

Resum

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.

Matèries

Oncogènesi, Cromatina, Epigenètica

Matèries (anglès)

Carcinogenesis, Chromatin, Epigenetics

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

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. 4D Genome rewiring during oncogene-induced and replicative senescende. _Molecular Cell_. 2020. Vol. 78, núm. 3, pàgs. 522-538. [consulta: 24 de gener de 2026]. ISSN: 1097-2765. [Disponible a: https://hdl.handle.net/2445/172030]

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