4D genome rewiring during oncogene-induced and replicative senescence

Sati, Satish; Serra, François; Castillo Andreo, David; Marti-Renom, Marc A.; Cavalli, Giacomo

4D genome rewiring during oncogene-induced and replicative senescence

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dc.contributor.author Sati, Satish
dc.contributor.author Serra, François
dc.contributor.author Castillo Andreo, David
dc.contributor.author Marti-Renom, Marc A.
dc.contributor.author Cavalli, Giacomo
dc.date.accessioned 2020-10-20T05:53:29Z
dc.date.available 2020-10-20T05:53:29Z
dc.date.issued 2020
dc.description.abstract 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.
dc.description.sponsorship Work at the M.A.M.-R. lab was supported by the European Research Council under the 7th Framework Program FP7/2007-2013 (ERC grant agreement 609989), the European Union’s Horizon 2020 research and innovation programme (grant agreement 676556), the Ministry of Economy and Competitiveness (BFU2017-85926-P), and the Agència de Gestió d’Ajuts Universitaris i de Recerca, AGAUR (SGR468). Work at CRG, BIST, and UPF was in part funded by the Spanish Ministry of Economy and Competitiveness, ‘‘Centro de Excelencia Severo Ochoa 2013-2017’’ (SEV-2012-0208), and ‘‘Centro de Excelencia María de Maeztu 2016-2019.’’ This article/publication is based upon work from COST Action CA18127, supported by COST (European Cooperation in Science and Technology)
dc.format.mimetype application/pdf
dc.identifier.citation Sati S, Bonev B, Szabo Q, Jost D, Bensadoun P, Serra F et al. V. Mol Cell. 2020 May 7; 78(3): 522-538.e9. DOI: 10.1016/j.molcel.2020.03.007
dc.identifier.doi http://dx.doi.org/10.1016/j.molcel.2020.03.007
dc.identifier.issn 1097-2765
dc.identifier.uri http://hdl.handle.net/10230/45513
dc.language.iso eng
dc.publisher Cell Press
dc.relation.ispartof Molecular Cell. 2020 May 7;78(3):522-38
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/676556
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-85926-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.other Genòmica
dc.subject.other Genètica
dc.subject.other Envelliment
dc.title 4D genome rewiring during oncogene-induced and replicative senescence
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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