Bibliographic Details
| Title: |
macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma. |
| Authors: |
Nikolic, Ana, Maule, Francesca, Bobyn, Anna, Ellestad, Katrina, Paik, Seungil, Marhon, Sajid A., Mehdipour, Parinaz, Lun, Xueqing, Chen, Huey-Miin, Mallard, Claire, Hay, Alexander J., Johnston, Michael J., Gafuik, Christopher J., Zemp, Franz J., Shen, Yaoqing, Ninkovic, Nicoletta, Osz, Katalin, Labit, Elodie, Berger, N. Daniel, Brownsey, Duncan K. |
| Source: |
Nature Communications; 5/27/2023, Vol. 14 Issue 1, p1-22, 22p |
| Subject Terms: |
GLIOBLASTOMA multiforme, EPIGENETICS, TRANSCRIPTION factors, METHYLGUANINE, CELL death, GLIOMAS |
| 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. Self-renewing cells play an important role in initiation, progression, and therapy resistance in glioblastoma. Here, the authors identify histone variant macroH2A2 as a regulator of chromatin organisation resulting in the suppression of transcriptional programs of self-renewal in glioblastoma. [ABSTRACT FROM AUTHOR] |
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| Database: |
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