ArticleScience advances2018
Multiple modes of PRC2 inhibition elicit global chromatin alterations in H3K27M pediatric glioma.
Article in Science advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
116 citing papers in PubMed, 189 citations in OpenAlex.
- A continuum-based reaction-diffusion model for spread of gene silencing in chromosomal inactivation.RNA (New York, N.Y.) · 2026Article
- Review
- Histone tail mutants: versatile tools for decoding chromatin, development, and disease.Trends in genetics : TIG · 2026Review
- Opposing function of AEBP2 isoforms fine-tune PRC2 catalytic activity.Nucleic acids research · 2026Article
- The conserved N-terminal SANT1-binding domain (SBD) of EZH2 regulates PRC2 activity.Genes & development · 2026Article
- PDS5A and TOP2B cooperate for chromatin recruitment via CTCF.bioRxiv : the preprint server for biology · 2026Article
- Deciphering the tumor microenvironment and role of immunotherapy in diffuse midline glioma: A scoping review.Neuro-oncology · 2026Article
- Comparative analyses of ChIP-seq, CUT&RUN and CUT&Tag for Polycomb chromatin profiling.BMB reports · 2026Article
- CBFA2T2: a novel H3K27 reader regulating metabolism and tumor growth.Molecular cancer · 2026Article
- Emerging structural insights into PRC2 function in development and disease.Trends in biochemical sciences · 2026Review
- H3K27me3-dependent imprinting and transcriptional regulation in early mouse embryos requires EZHIP-mediated restriction of PRC2 activity.Nature communications · 2026Article
- Transcriptomics-guided high-throughput drug screening identifies potent therapies for P53 pathway altered DIPG/DMG.Neuro-oncology · 2026Article
- Novel modifiers of oncoprotein-mediated Polycomb inhibition in Drosophila melanogaster.Genetics · 2025Article
- A histone methyltransferase-independent function of PRC2 controls small RNA dynamics during programmed DNA elimination in Paramecium.Nucleic acids research · 2025Article
- Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1.Cell reports · 2025Article
- The Bermuda Triangle of paediatric brain cancers: epigenetics, developmental timing window and cell of origin.Cancer metastasis reviews · 2025Review
- Genetic Markers and Mutations in Primary Spinal Cord Tumors and Their Impact on Clinical Management.Brain sciences · 2025Review
- Aberrant EZHIP expression drives tumorigenesis in osteosarcoma.Nature communications · 2025Article
- Investigating oncoprotein-mediated chromatin dysregulation inbioRxiv : the preprint server for biology · 2025Article
- H3F3A K27M mutations drive a repressive transcriptome by modulating chromatin accessibility independent of H3K27me3 in Diffuse Midline Glioma.Epigenetics & chromatin · 2025Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
A methionine substitution at lysine-27 on histone H3 variants (H3K27M) characterizes ~80% of diffuse intrinsic pontine gliomas (DIPG) and inhibits polycomb repressive complex 2 (PRC2) in a dominant-negative fashion. Yet, the mechanisms for this inhibition and abnormal epigenomic landscape have not been resolved. Using quantitative proteomics, we discovered that robust PRC2 inhibition requires levels of H3K27M greatly exceeding those of PRC2, seen in DIPG. While PRC2 inhibition requires interaction with H3K27M, we found that this interaction on chromatin is transient, with PRC2 largely being released from H3K27M. Unexpectedly, inhibition persisted even after PRC2 dissociated from H3K27M-containing chromatin, suggesting a lasting impact on PRC2. Furthermore, allosterically activated PRC2 is particularly sensitive to H3K27M, leading to the failure to spread H3K27me from PRC2 recruitment sites and consequently abrogating PRC2's ability to establish H3K27me2-3 repressive chromatin domains. In turn, levels of polycomb antagonists such as H3K36me2 are elevated, suggesting a more global, downstream effect on the epigenome. Together, these findings reveal the conditions required for H3K27M-mediated PRC2 inhibition and reconcile seemingly paradoxical effects of H3K27M on PRC2 recruitment and activity.
Indexed as
Identifiers
What OpenQuestion holds
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.