macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 05 2023
27 05 2023
Historique:
received:
19
11
2021
accepted:
22
05
2023
medline:
29
5
2023
pubmed:
28
5
2023
entrez:
27
5
2023
Statut:
epublish
Résumé
Self-renewal is a crucial property of glioblastoma cells that is enabled by the choreographed functions of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could therefore represent an important step toward developing effective treatments for this universally lethal cancer. Here we uncover an epigenetic axis of self-renewal mediated by the histone variant macroH2A2. With omics and functional assays deploying patient-derived in vitro and in vivo models, we show that macroH2A2 shapes chromatin accessibility at enhancer elements to antagonize transcriptional programs of self-renewal. macroH2A2 also sensitizes cells to small molecule-mediated cell death via activation of a viral mimicry response. Consistent with these results, our analyses of clinical cohorts indicate that high transcriptional levels of this histone variant are associated with better prognosis of high-grade glioma patients. Our results reveal a targetable epigenetic mechanism of self-renewal controlled by macroH2A2 and suggest additional treatment approaches for glioblastoma patients.
Identifiants
pubmed: 37244935
doi: 10.1038/s41467-023-38919-2
pii: 10.1038/s41467-023-38919-2
pmc: PMC10224928
doi:
Substances chimiques
Histones
0
Chromatin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3062Subventions
Organisme : CIHR
ID : PJT-156278
Pays : Canada
Informations de copyright
© 2023. The Author(s).
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