ArticleProceedings of the National Academy of Sciences of the United States of America2019
PRC2 engages a bivalent H3K27M-H3K27me3 dinucleosome inhibitor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 45 citations in OpenAlex.
- FTO Controls Endometrial Receptivity and Embryo Implantation through Regulating mCommunications biology · 2026Article
- Emerging structural insights into PRC2 function in development and disease.Trends in biochemical sciences · 2026Review
- Novel modifiers of oncoprotein-mediated Polycomb inhibition in Drosophila melanogaster.Genetics · 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
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- Pediatric Diffuse Midline Glioma H3K27-Altered: From Developmental Origins to Therapeutic Challenges.Cancers · 2024Review
- H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in pediatric high-grade glioma cells.Cell reports · 2024Article
- Design principles of 3D epigenetic memory systems.Science (New York, N.Y.) · 2023Article
- BRCA1-BARD1 combines multiple chromatin recognition modules to bridge nascent nucleosomes.Nucleic acids research · 2023Article
- Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas.Cell reports. Medicine · 2023Article
- Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma.Cancer metastasis reviews · 2023Review
- Chemical Biology Approaches to Identify and Profile Interactors of Chromatin Modifications.ACS chemical biology · 2023Review
- CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site.Nature communications · 2022Article
- Oncohistones: Exposing the nuances and vulnerabilities of epigenetic regulation.Molecular cell · 2022Review
- Oncohistones: Hijacking the histone code.Annual review of cancer biology · 2022Article
- A Genetically Encoded Approach for Breaking Chromatin Symmetry.ACS central science · 2022Article
- PRC2, Chromatin Regulation, and Human Disease: Insights From Molecular Structure and Function.Frontiers in oncology · 2022Review
- The Profiles of Tet-Mediated DNA Hydroxymethylation in Human Gliomas.Frontiers in oncology · 2022Article
- Simultaneous disruption of PRC2 and enhancer function underlies histone H3.3-K27M oncogenic activity in human hindbrain neural stem cells.Nature genetics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
A lysine-to-methionine mutation at lysine 27 of histone 3 (H3K27M) has been shown to promote oncogenesis in a subset of pediatric gliomas. While there is evidence that this "oncohistone" mutation acts by inhibiting the histone methyltransferase PRC2, the details of this proposed mechanism nevertheless continue to be debated. Recent evidence suggests that PRC2 must simultaneously bind both H3K27M and H3K27me3 to experience competitive inhibition of its methyltransferase activity. In this work, we used PRC2 inhibitor treatments in a transgenic H3K27M cell line to validate this dependence in a cellular context. We further used designer chromatin inhibitors to probe the geometric constraints of PRC2 engagement of H3K27M and H3K27me3 in a biochemical setting. We found that PRC2 binds to a bivalent inhibitor unit consisting of an H3K27M and an H3K27me3 nucleosome and exhibits a distance dependence in its affinity for such an inhibitor, which favors closer proximity of the 2 nucleosomes within a chromatin array. Together, our data precisely delineate fundamental aspects of the H3K27M inhibitor and support a model wherein PRC2 becomes trapped at H3K27M-H3K27me3 boundaries.
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.