ArticleeLife2018
H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 102 citations in OpenAlex.
- Histone tail mutants: versatile tools for decoding chromatin, development, and disease.Trends in genetics : TIG · 2026Review
- Histone modifications across cancers: mechanisms, therapy and clinical translation.Molecular cancer · 2026Review
- From Classical to Emerging Biomarkers of Brain and Central Nervous System Tumors. An Evidence-Based Review with a Focus on Gliomas.Cellular and molecular neurobiology · 2026Review
- Inhibiting sirtuin-dependent DNA repair and oxidative stress responses impairs DIPG cell survival.Research square · 2025Article
- The Bermuda Triangle of paediatric brain cancers: epigenetics, developmental timing window and cell of origin.Cancer metastasis reviews · 2025Review
- The proteomic landscape of diffuse midline glioma highlights the therapeutic potential of non-histone protein methyltransferases.Neuro-oncology · 2025Article
- 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
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- PALB2 deficiency may sensitize H3K27M-mutant pediatric HGG cells to BMN673/talazoparib.Frontiers in oncology · 2025Article
- Epigenetic reprogramming in pediatric gliomas: from molecular mechanisms to therapeutic implications.Trends in cancer · 2024Review
- CHD2 Regulates Neuron-Glioma Interactions in Pediatric Glioma.Cancer discovery · 2024Article
- H3K27M mutant glioma: Disease definition and biological underpinnings.Neuro-oncology · 2024Review
- EZH2 mutations in follicular lymphoma distort H3K27me3 profiles and alter transcriptional responses to PRC2 inhibition.Nature communications · 2024Article
- H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in pediatric high-grade glioma cells.Cell reports · 2024Article
- A mouse model of Weaver syndrome displays overgrowth and excess osteogenesis reversible with KDM6A/6B inhibition.JCI insight · 2024Article
- Histone mutations in cancer.Biochemical Society transactions · 2023Article
- Radiotherapy and radio-sensitization in H3CNS neuroscience & therapeutics · 2023Review
- Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics.Hereditas · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Expression of histone H3.3K27M mutant proteins in human diffuse intrinsic pontine glioma (DIPG) results in a global reduction of tri-methylation of H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds of genomic loci, a dichotomous change that lacks mechanistic insights. Here, we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. Moreover, the levels of H3.3K27M proteins are low at the retained H3K27me3 peaks and consequently having minimal effects on the PRC2 activity at these loci. H3K27me3-mediated silencing at specific tumor suppressor genes, including Wilms Tumor 1, promotes proliferation of DIPG cells. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and contributes to tumorigenesis in part by locally enhancing H3K27me3, and hence silencing of tumor suppressor genes.
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Registered trials
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.