Loss of CBX2 induces genome instability and senescence-associated chromosomal rearrangements.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
02 11 2020
02 11 2020
Historique:
received:
22
10
2019
revised:
08
06
2020
accepted:
02
08
2020
entrez:
2
9
2020
pubmed:
2
9
2020
medline:
31
3
2021
Statut:
ppublish
Résumé
The polycomb group protein CBX2 is an important epigenetic reader involved in cell proliferation and differentiation. While CBX2 overexpression occurs in a wide range of human tumors, targeted deletion results in homeotic transformation, proliferative defects, and premature senescence. However, its cellular function(s) and whether it plays a role in maintenance of genome stability remain to be determined. Here, we demonstrate that loss of CBX2 in mouse fibroblasts induces abnormal large-scale chromatin structure and chromosome instability. Integrative transcriptome analysis and ATAC-seq revealed a significant dysregulation of transcripts involved in DNA repair, chromocenter formation, and tumorigenesis in addition to changes in chromatin accessibility of genes involved in lateral sclerosis, basal transcription factors, and folate metabolism. Notably, Cbx2-/- cells exhibit prominent decondensation of satellite DNA sequences at metaphase and increased sister chromatid recombination events leading to rampant chromosome instability. The presence of extensive centromere and telomere defects suggests a prominent role for CBX2 in heterochromatin homeostasis and the regulation of nuclear architecture.
Identifiants
pubmed: 32870972
pii: 152063
doi: 10.1083/jcb.201910149
pmc: PMC7594495
pii:
doi:
Substances chimiques
Cbx2 protein, mouse
0
Chromatin
0
Polycomb Repressive Complex 1
EC 2.3.2.27
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NICHD NIH HHS
ID : R56 HD093383
Pays : United States
Informations de copyright
© 2020 Baumann et al.
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