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

Molecular cell (2020-03-30)
Satish Sati, Boyan Bonev, Quentin Szabo, Daniel Jost, Paul Bensadoun, Francois Serra, Vincent Loubiere, Giorgio Lucio Papadopoulos, Juan-Carlos Rivera-Mulia, Lauriane Fritsch, Pauline Bouret, David Castillo, Josep Ll Gelpi, Modesto Orozco, Cedric Vaillant, Franck Pellestor, Frederic Bantignies, Marc A Marti-Renom, David M Gilbert, Jean-Marc Lemaitre, Giacomo Cavalli
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.

MATERIALS
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Product Description

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MISSION® esiRNA, targeting human DNMT1

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