4D Genome Rewiring during Oncogene-Induced and Replicative Senescence

Title4D Genome Rewiring during Oncogene-Induced and Replicative Senescence
Publication TypeJournal Article
Year of Publication2020
AuthorsSati, Satish, Bonev Boyan, Szabo Quentin, Jost Daniel, Bensadoun Paul, Serra Francois, Loubiere Vincent, Papadopoulos Giorgio Lucio, Rivera-Mulia Juan-Carlos, Fritsch Lauriane, Bouret Pauline, Castillo David, Gelpi Josep Ll., Orozco Modesto, Vaillant Cedric, Pellestor Franck, Bantignies Frederic, Marti-Renom Marc A., Gilbert David M., Lemaitre Jean-Marc, and Cavalli Giacomo
JournalMolecular Cell
Pagination522 - 538.e9
Date Published07/2020
ISBN Number1097-2765
Keywords3D genome architecture, chromatin compartments, DNMT1, gene regulation, Hi-C, oncogene-induced senescence, replicative senescence, senescence

SummaryTo 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.

Short TitleMolecular Cell