4D Genome Rewiring during Oncogene-Induced and Replicative Senescence.
3D genome architecture
DNMT1
Hi-C
chromatin compartments
gene regulation
oncogene-induced senescence
replicative senescence
senescence
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
07 05 2020
07 05 2020
Historique:
received:
16
05
2019
revised:
20
12
2019
accepted:
04
03
2020
pubmed:
30
3
2020
medline:
29
8
2020
entrez:
30
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32220303
pii: S1097-2765(20)30155-6
doi: 10.1016/j.molcel.2020.03.007
pmc: PMC7208559
pii:
doi:
Substances chimiques
Heterochromatin
0
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
DNMT1 protein, human
EC 2.1.1.37
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
522-538.e9Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM083337
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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