Sati, SatishBonev, BoyanSzabo, QuentinJost, DanielBensadoun, PaulSerra, FrancoisLoubiere, VincentPapadopoulos, Giorgio LucioRivera-Mulia, Juan-CarlosFrisch, LaurianeBouret, PaulineCastillo, DavidGelpí Buchaca, Josep LluísOrozco López, ModestoVaillant, CedricPellestor, FranckBantignies, FredericMartí Renom, Marc A.Gilbert, David M.Lemaitre, Jean-MarcCavalli, Giacomo2020-11-122020-11-122020-05-071097-2765https://hdl.handle.net/2445/172030To 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.17 p.application/pdfengcc-by-nc-nd (c) Elsevier, 2020http://creativecommons.org/licenses/by-nc-nd/3.0/esOncogènesiCromatinaEpigenèticaCarcinogenesisChromatinEpigeneticsinfo:eu-repo/semantics/article7024882020-11-12info:eu-repo/semantics/openAccess32220303