ArticleCommunications biology2020
Reciprocal H3.3 gene editing identifies K27M and G34R mechanisms in pediatric glioma including NOTCH signaling.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Evidence for coordinate CTCF and histone H3.3 activities in K27M diffuse midline gliomas.Acta neuropathologica communications · 2026Article
- Modeling gliomas with organoids: reconstructing the human neural microenvironment for translational neuro-oncology.Frontiers in oncology · 2026Review
- 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
- Role of epigenetics in paediatric cancer pathogenesis & drug resistance.British journal of cancer · 2025Review
- H3F3A K27M mutations drive a repressive transcriptome by modulating chromatin accessibility independent of H3K27me3 in Diffuse Midline Glioma.Epigenetics & chromatin · 2025Article
- The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis.Current biology : CB · 2025Article
- Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities.Journal of translational medicine · 2025Review
- Super-enhancer inhibitors THZ2 and JQ1 reverse temozolomide resistance in glioblastoma by suppressing SE-driven SOX9 expression.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Roles of Histone H2B, H3 and H4 Variants in Cancer Development and Prognosis.International journal of molecular sciences · 2024Review
- Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors.Nucleic acids research · 2024Article
- H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in pediatric high-grade glioma cells.Cell reports · 2024Article
- Emerging roles of cancer-associated histone mutations in genomic instabilities.Frontiers in cell and developmental biology · 2024Review
- Therapeutically targeting the unique disease landscape of pediatric high-grade gliomas.Frontiers in oncology · 2024Review
- Brain Tumors: Development, Drug Resistance, and Sensitization - An Epigenetic Approach.Epigenetics · 2023Review
- Knockout tales: the versatile roles of histone H3.3 in development and disease.Epigenetics & chromatin · 2023Review
- Pediatric Central Nervous System Tumor Overview and Emerging Treatment Considerations.Brain sciences · 2023Review
- Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma.Cancer metastasis reviews · 2023Review
- Response to: Correspondence on 'H3.3K27M mutation is not a suitable target for immunotherapy in HLA-A2+ patients with diffuse midline glioma' by ChhedaJournal for immunotherapy of cancer · 2023Article
- A knockout-first model of H3f3a gene targeting leads to developmental lethality.Genesis (New York, N.Y. : 2000) · 2023Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Histone H3.3 mutations are a hallmark of pediatric gliomas, but their core oncogenic mechanisms are not well-defined. To identify major effectors, we used CRISPR-Cas9 to introduce H3.3K27M and G34R mutations into previously H3.3-wildtype brain cells, while in parallel reverting the mutations in glioma cells back to wildtype. ChIP-seq analysis broadly linked K27M to altered H3K27me3 activity including within super-enhancers, which exhibited perturbed transcriptional function. This was largely independent of H3.3 DNA binding. The K27M and G34R mutations induced several of the same pathways suggesting key shared oncogenic mechanisms including activation of neurogenesis and NOTCH pathway genes. H3.3 mutant gliomas are also particularly sensitive to NOTCH pathway gene knockdown and drug inhibition, reducing their viability in culture. Reciprocal editing of cells generally produced reciprocal effects on tumorgenicity in xenograft assays. Overall, our findings define common and distinct K27M and G34R oncogenic mechanisms, including potentially targetable pathways.
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