ArticleMolecular cell2018
Allosteric Activation Dictates PRC2 Activity Independent of Its Recruitment to Chromatin.
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
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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.
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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.
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Who cites it
80 citing papers in PubMed, 135 citations in OpenAlex.
- A continuum-based reaction-diffusion model for spread of gene silencing in chromosomal inactivation.RNA (New York, N.Y.) · 2026Article
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- A maternal Polycomb imprint is maintained in early Drosophila development through lower-order methylation states.Cell reports · 2026Article
- Oncogenic Ras drives EED degradation and PRC2 dysfunction to promote aggressive squamous cell carcinoma.Nature communications · 2026Article
- Opposing function of AEBP2 isoforms fine-tune PRC2 catalytic activity.Nucleic acids research · 2026Article
- The role of the WD40-repeat protein family in cancer.Molecular cancer · 2026Review
- Integrating network toxicology with multi-omics approaches to elucidate molecular targets and pathway mechanisms in BPA-induced hepatocellular carcinoma.Molecular diversity · 2026Article
- The conserved N-terminal SANT1-binding domain (SBD) of EZH2 regulates PRC2 activity.Genes & development · 2026Article
- Comparative analyses of ChIP-seq, CUT&RUN and CUT&Tag for Polycomb chromatin profiling.BMB reports · 2026Article
- Dominant-negative effects of Weaver syndrome-associated EZH2 variants.Genes & development · 2025Article
- The role of ASXL1, SRSF2, and EZH2 mutations in chromatin dysregulation of myelodysplastic neoplasia and acute myeloid leukemia.Leukemia · 2025Review
- Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1.Cell reports · 2025Article
- Protocol for reconstituting enzymatic activities for ultra-large histone methyltransferases NSD1 and SETD2 using a baculovirus expression system.STAR protocols · 2025Article
- Functional analysis of human EED variants using Drosophila.Genetics · 2025Article
- The Notch pathway: A guardian of cell fate during neurogenesis.Current opinion in cell biology · 2025Review
- Lower-order methylation states underlie the maintenance and re-establishment of Polycomb modifications inbioRxiv : the preprint server for biology · 2025Article
- Structure-guided design and development of cyclic peptide allosteric activators of Polycomb Repressive Complex 2.bioRxiv : the preprint server for biology · 2025Article
- Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications.Nature structural & molecular biology · 2025Article
- Replication-coupled inheritance of chromatin states.Cell insight · 2024Review
20 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
10 authors at 4 institutions in 1 country.
Funding
Abstract
PRC2 is a therapeutic target for several types of cancers currently undergoing clinical trials. Its activity is regulated by a positive feedback loop whereby its terminal enzymatic product, H3K27me3, is specifically recognized and bound by an aromatic cage present in its EED subunit. The ensuing allosteric activation of the complex stimulates H3K27me3 deposition on chromatin. Here we report a stepwise feedback mechanism entailing key residues within distinctive interfacing motifs of EZH2 or EED that are found to be mutated in cancers and/or Weaver syndrome. PRC2 harboring these EZH2 or EED mutants manifested little activity in vivo but, unexpectedly, exhibited similar chromatin association as wild-type PRC2, indicating an uncoupling of PRC2 activity and recruitment. With genetic and chemical tools, we demonstrated that targeting allosteric activation overrode the gain-of-function effect of EZH2
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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.