Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/172030
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 Cromatina Epigenètica Carcinogenesis Chromatin Epigenetics |
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: https://doi.org/10.1016/j.molcel.2020.03.007 |
It is part of: | Molecular Cell, 2020, vol. 78, num. 3, p. 522-538 |
URI: | http://hdl.handle.net/2445/172030 |
Related resource: | https://doi.org/10.1016/j.molcel.2020.03.007 |
ISSN: | 1097-2765 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
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