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You are here: Home / Teams / Physical Biology of Chromatin - D. Jost / Publications / 4D Genome Rewiring during Oncogene-Induced and Replicative Senescence.

4D Genome Rewiring during Oncogene-Induced and Replicative Senescence.

Satish Sati, Boyan Bonev, Quentin Szabo, Daniel Jost, Paul Bensadoun, Francois Serra, Vincent Loubiere, Giorgio L Papadopoulos, Juan-Carlos Rivera-Mulia, Lauriane Fritsch, Pauline Bouret, David Castillo, Josep L Gelpi, Modesto Orozco, Cedric Vaillant, Franck Pellestor, Frederic Bantignies, Marc A Marti-Renom, David M Gilbert, Jean-Marc Lemaitre, and Giacomo Cavalli (2020)

Mol Cell, 78(3):522-538.e9.

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. ThisOIS-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 canidentify critical features of RS and OIS and discover determinants of acute senescence and SAHF formation.

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