Evidence map›Paper›PMID 39303719›Full record

ArticleMolecular cell2024

Activation of automethylated PRC2 by dimerization on chromatin.

Paul V Sauer, Egor Pavlenko, Trinity Cookis, Linda C Zirden, Juliane Renn, Ankush Singhal, Pascal Hunold, Michaela N Hoehne-Wiechmann, Olivia van Ray, Farnusch Kaschani and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Exchange dynamics and kinetic control of gene regulation complexes.Nature reviews. Molecular cell biology · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Paul V SauerCalifornia Institute for Quantitative Biology (QB3), University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
Egor PavlenkoCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany.
Trinity CookisDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Linda C ZirdenCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany.
Juliane RennCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany.
Ankush SinghalTheoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Pascal HunoldCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Michaela N Hoehne-WiechmannCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Olivia van RayCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Farnusch KaschaniDepartment of Chemical Biology, University of Duisburg-Essen, Center for Medical Biotechnology (ZMB), Faculty of Biology, Essen, Germany.
Markus KaiserDepartment of Chemical Biology, University of Duisburg-Essen, Center for Medical Biotechnology (ZMB), Faculty of Biology, Essen, Germany.
Robert Hänsel-HertschCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Institute of Human Genetics, University Hospital Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
Karissa Y SanbonmatsuTheoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Eva NogalesCalifornia Institute for Quantitative Biology (QB3), University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: enogales@lbl.gov.
Simon PoepselCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany. Electronic address: spoepsel@uni-koeln.de.

Funding

ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
Structural studies of function and regulation of microtubules and transcriptional gene expression machineryR35GM127018 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Eva Nogales · 2018 to 2026
$4.3M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM129325NIGMS NIH HHS R35 GM127018
6 · The paper itself

Abstract

Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 is associated with transcriptionally repressed chromatin and is established when PRC2 is allosterically activated upon methyl-lysine binding by the regulatory subunit EED. Automethylation of the catalytic subunit enhancer of zeste homolog 2 (EZH2) stimulates its activity by an unknown mechanism. Here, we show that human PRC2 forms a dimer on chromatin in which an inactive, automethylated PRC2 protomer is the allosteric activator of a second PRC2 that is poised to methylate H3 of a substrate nucleosome. Functional assays support our model of allosteric trans-autoactivation via EED, suggesting a previously unknown mechanism mediating context-dependent activation of PRC2. Our work showcases the molecular mechanism of auto-modification-coupled dimerization in the regulation of chromatin-modifying complexes.

Indexed as

ChromatinEnhancer of Zeste Homolog 2 ProteinHistonesPolycomb Repressive Complex 2Protein MultimerizationAllosteric RegulationHEK293 CellsHumansMethylationNucleosomesProtein BindingChromatinEED protein, humanEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesNucleosomesPolycomb Repressive Complex 2chromatincryo-EMdevelopmentepigeneticsgene regulationhistone methyltransferasePRC2trans-activation

Identifiers

PMID39303719
PMCPMC11980035

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.