macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma

Ana Nikolic, Francesca Maule, Anna Bobyn, Katrina Ellestad, Seungil Paik, Sajid A. Marhon, Parinaz Mehdipour, Xueqing Lun, Huey-Miin Chen, Claire Mallard, Alexander J. Hay, Michael J. Johnston, Christopher J. Gafuik, Franz J. Zemp, Yaoqing Shen, Nicoletta Ninkovic, Katalin Osz, Elodie Labit, N. Daniel Berger, Duncan K. Brownsey, John J. Kelly, Jeff Biernaskie, Peter B. Dirks, Darren J. Derksen, Steven J. M. Jones, Donna L. Senger, Jennifer A. Chan, Douglas J. Mahoney, Daniel D. Carvalho and Marco Gallo ()
Additional contact information
Ana Nikolic: University of Calgary
Francesca Maule: University of Calgary
Anna Bobyn: University of Calgary
Katrina Ellestad: University of Calgary
Seungil Paik: University of Calgary
Sajid A. Marhon: Princess Margaret Cancer Centre
Parinaz Mehdipour: Princess Margaret Cancer Centre
Xueqing Lun: University of Calgary
Huey-Miin Chen: University of Calgary
Claire Mallard: University of Calgary
Alexander J. Hay: University of Calgary
Michael J. Johnston: University of Calgary
Christopher J. Gafuik: University of Calgary
Franz J. Zemp: University of Calgary
Yaoqing Shen: BC Cancer
Nicoletta Ninkovic: University of Calgary
Katalin Osz: University of Calgary
Elodie Labit: University of Calgary
N. Daniel Berger: University of Calgary
Duncan K. Brownsey: University of Calgary
John J. Kelly: University of Calgary
Jeff Biernaskie: University of Calgary
Peter B. Dirks: Hospital for Sick Children
Darren J. Derksen: University of Calgary
Steven J. M. Jones: BC Cancer
Donna L. Senger: University of Calgary
Jennifer A. Chan: University of Calgary
Douglas J. Mahoney: University of Calgary
Daniel D. Carvalho: Princess Margaret Cancer Centre
Marco Gallo: University of Calgary

Nature Communications, 2023, vol. 14, issue 1, 1-22

Abstract: Abstract 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38919-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38919-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38919-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().