ArticleProceedings of the National Academy of Sciences of the United States of America2020
Histone H3.3 G34 mutations promote aberrant PRC2 activity and drive tumor progression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 95 citations in OpenAlex.
- Review
- O-SNAP uncovers nanoscale chromatin remodeling in dedifferentiation and stress responses.Nature communications · 2026Article
- Establishment and characterization of NCC-GCTB16-C1: novel patient-derived cell line of giant cell tumor of bone.Human cell · 2026Article
- Giant Cell Tumor of Bone: Biology, Pathophysiology, and Histopathology in the Era of H3F3A.Biomedicines · 2026Review
- Divergent molecular pathways drive monomorphic epitheliotropic and enteropathy-associated intestinal T-cell lymphoma.Leukemia · 2026Article
- Case Report: Identification of rareFrontiers in oncology · 2026Article
- Novel modifiers of oncoprotein-mediated Polycomb inhibition in Drosophila melanogaster.Genetics · 2025Article
- The Bermuda Triangle of paediatric brain cancers: epigenetics, developmental timing window and cell of origin.Cancer metastasis reviews · 2025Review
- A review of diffuse hemispheric glioma, H3 G34-mutant disease development, DNA repair, microenvironment, and treatments on the horizon.NPJ precision oncology · 2025Review
- Investigating oncoprotein-mediated chromatin dysregulation inbioRxiv : the preprint server for biology · 2025Article
- Role of epigenetics in paediatric cancer pathogenesis & drug resistance.British journal of cancer · 2025Review
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- Histone H3E50K remodels chromatin to confer oncogenic activity and support an EMT phenotype.NAR cancer · 2025Article
- Multifunctional histone variants in genome function.Nature reviews. Genetics · 2025Review
- Characterization of oncohistone H2B variants in Schizosaccharomyces pombe reveals a key role of H2B monoubiquitination deficiency in genomic instability by altering gene expression.FEMS yeast research · 2025Article
- The Role of Chronic Inflammation in Pediatric Cancer.Cancers · 2025Review
- IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma.Targeted oncology · 2025Review
- (B)On(e)-cohistones and the epigenetic alterations at the root of bone cancer.Cell death and differentiation · 2025Review
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- Histone H3 mutations and their impact on genome stability maintenance.Biochemical Society transactions · 2024Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
A high percentage of pediatric gliomas and bone tumors reportedly harbor missense mutations at glycine 34 in genes encoding histone variant H3.3. We find that these H3.3 G34 mutations directly alter the enhancer chromatin landscape of mesenchymal stem cells by impeding methylation at lysine 36 on histone H3 (H3K36) by SETD2, but not by the NSD1/2 enzymes. The reduction of H3K36 methylation by G34 mutations promotes an aberrant gain of PRC2-mediated H3K27me2/3 and loss of H3K27ac at active enhancers containing SETD2 activity. This altered histone modification profile promotes a unique gene expression profile that supports enhanced tumor development in vivo. Our findings are mirrored in G34W-containing giant cell tumors of bone where patient-derived stromal cells exhibit gene expression profiles associated with early osteoblastic differentiation. Overall, we demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors.
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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.