ArticleNature genetics2021
Simultaneous disruption of PRC2 and enhancer function underlies histone H3.3-K27M oncogenic activity in human hindbrain neural stem cells.
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 71 citations in OpenAlex.
- Synergistic cell-cycle repression by HDAC/EZH2 co-targeting in H3K27-altered diffuse midline glioma.Molecular therapy. Oncology · 2026Article
- Histone tail mutants: versatile tools for decoding chromatin, development, and disease.Trends in genetics : TIG · 2026Review
- H3K27me3 spreading organizes canonical PRC1 chromatin architecture to regulate developmental programs.Nature genetics · 2026Article
- Cancer stem cells synthesize proline to attenuate oxidative stress.The Journal of clinical investigation · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- RNA N6-methyladenosine (m6A) regulates cell cycle progression in diffuse midline glioma (DMG) and confers sensitivity to FTO inhibition.Cell death & disease · 2026Article
- CBFA2T2: a novel H3K27 reader regulating metabolism and tumor growth.Molecular cancer · 2026Article
- Modeling pediatric brain tumors with human stem cells.Frontiers in cellular neuroscience · 2026Review
- Metabolic Interplay in Acute Lung Injury: PARK7 Integrates FADS1/2-Dependent PUFA Metabolism and H3K14 Lactylation to Attenuate Endothelial Ferroptosis and Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Bermuda Triangle of paediatric brain cancers: epigenetics, developmental timing window and cell of origin.Cancer metastasis reviews · 2025Review
- Article
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Aberrant EZHIP expression drives tumorigenesis in osteosarcoma.Nature communications · 2025Article
- Current Landscape of Preclinical Models for Pediatric Gliomas: Clinical Implications and Future Directions.Cancers · 2025Review
- A specific form of cPRC1 containing CBX4 is co-opted to mediate oncogenic gene repression in diffuse midline glioma.Molecular cell · 2025Article
- H3F3A K27M mutations drive a repressive transcriptome by modulating chromatin accessibility independent of H3K27me3 in Diffuse Midline Glioma.Epigenetics & chromatin · 2025Article
- Article
- An oncohistone-driven H3.3K27M/CREB5/ID1 axis maintains the stemness and malignancy of diffuse intrinsic pontine glioma.Nature communications · 2025Article
- Multifunctional histone variants in genome function.Nature reviews. Genetics · 2025Review
- A conserved switch to less catalytically active Polycomb repressive complexes in non-dividing cells.Cell reports · 2025Article
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
Driver mutations in genes encoding histone H3 proteins resulting in p.Lys27Met substitutions (H3-K27M) are frequent in pediatric midline brain tumors. However, the precise mechanisms by which H3-K27M causes tumor initiation remain unclear. Here, we use human hindbrain neural stem cells to model the consequences of H3.3-K27M on the epigenomic landscape in a relevant developmental context. Genome-wide mapping of epitope-tagged histone H3.3 revealed that both the wild type and the K27M mutant incorporate abundantly at pre-existing active enhancers and promoters, and to a lesser extent at Polycomb repressive complex 2 (PRC2)-bound regions. At active enhancers, H3.3-K27M leads to focal H3K27ac loss, decreased chromatin accessibility and reduced transcriptional expression of nearby neurodevelopmental genes. In addition, H3.3-K27M deposition at a subset of PRC2 target genes leads to increased PRC2 and PRC1 binding and augmented transcriptional repression that can be partially reversed by PRC2 inhibitors. Our work suggests that, rather than imposing de novo transcriptional circuits, H3.3-K27M drives tumorigenesis by locking initiating cells in their pre-existing, immature epigenomic state, via disruption of PRC2 and enhancer functions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.