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Title: 4D Genome rewiring during oncogene-induced and replicative senescende
Author: Sati, Satish
Bonev, Boyan
Szabo, Quentin
Jost, Daniel
Bensadoun, Paul
Serra, Francois
Loubiere, Vincent
Papadopoulos, Giorgio Lucio
Rivera-Mulia, Juan-Carlos
Frisch, Lauriane
Bouret, Pauline
Castillo, David
Gelpí Buchaca, Josep Lluís
Orozco López, Modesto
Vaillant, Cedric
Pellestor, Franck
Bantignies, Frederic
Marti Renom, Marc A.
Gilbert, David M.
Lemaitre, Jean-Marc
Cavalli, Giacomo
Keywords: Oncogènesi
Issue Date: 7-May-2020
Publisher: Cell Press
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.
Note: Versió postprint del document publicat a:
It is part of: Molecular Cell, 2020, vol. 78, num. 3, p. 522-538
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ISSN: 1097-2765
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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