Evidence map›Paper›PMID 31488577›Full record

ArticleGenes & development2019

Automethylation of PRC2 promotes H3K27 methylation and is impaired in H3K27M pediatric glioma.

Chul-Hwan Lee, Jia-Ray Yu, Jeffrey Granat, Ricardo Saldaña-Meyer, Joshua Andrade, Gary LeRoy, Ying Jin, Peder Lund, James M Stafford, Benjamin A Garcia and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing 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

71 citing papers in PubMed, 115 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Dissecting polycomb complexes for enhanced fetal hemoglobin production.bioRxiv : the preprint server for biology · 2026
    Article
  5. PDS5A and TOP2B cooperate for chromatin recruitment via CTCF.bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. EZH2,World journal of stem cells · 2025
    Article
  12. Article
  13. Review
  14. An E2 ubiquitin-conjugating enzyme links diubiquitinated H2B to H3K27M oncohistone function.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Molecular and Pathological Features of Paediatric High-Grade Gliomas.International journal of molecular sciences · 2024
    Review
  17. Article
  18. Article
  19. Review
  20. Review

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Chul-Hwan Lee *Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.ORCID 0000-0003-0643-0100
Jia-Ray Yu *Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.ORCID 0000-0002-7080-4333
Jeffrey Granat *Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.
Ricardo Saldaña-MeyerDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.ORCID 0000-0001-8431-2682
Joshua AndradeProteomics Laboratory, New York University School of Medicine, New York, New York 10016, USA.
Gary LeRoyDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.
Ying JinShared Bioinformatics Core, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Peder LundDepartment of Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
James M StaffordDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.
Benjamin A GarciaDepartment of Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.ORCID 0000-0002-2306-1207
Beatrix UeberheideProteomics Laboratory, New York University School of Medicine, New York, New York 10016, USA.ORCID 0000-0003-2512-0204
Danny ReinbergDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.ORCID 0000-0003-4288-2016
Howard Hughes Medical Institute · USAbterra Biosciences (United States) · USUniversity of Pennsylvania · USCold Spring Harbor Laboratory · US

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1M
Shared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6M
IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1M
Repression via Facultative HeterochromatinR01CA199652 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI REINBERG, DANNY · 2015 to 2025
$4.2M
Understanding the Role of Combinatorial Histone PTM PatternsR01GM110174 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI GARCIA, BENJAMIN A · 2014 to 2017
$1.3M
AUTS2 and the chromatin dynamics of alcohol use disordersK99AA024837 · NIAAA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI STAFFORD, JAMES M · 2017 to 2018
$328k
Howard Hughes Medical InstituteNCI NIH HHS P01 CA196539NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA199652NCI NIH HHS T32 CA009140NIAAA NIH HHS K99 AA024837NIGMS NIH HHS R01 GM110174
6 · The paper itself

Abstract

The histone methyltransferase activity of PRC2 is central to the formation of H3K27me3-decorated facultative heterochromatin and gene silencing. In addition, PRC2 has been shown to automethylate its core subunits, EZH1/EZH2 and SUZ12. Here, we identify the lysine residues at which EZH1/EZH2 are automethylated with EZH2-K510 and EZH2-K514 being the major such sites in vivo. Automethylated EZH2/PRC2 exhibits a higher level of histone methyltransferase activity and is required for attaining proper cellular levels of H3K27me3. While occurring independently of PRC2 recruitment to chromatin, automethylation promotes PRC2 accessibility to the histone H3 tail. Intriguingly, EZH2 automethylation is significantly reduced in diffuse intrinsic pontine glioma (DIPG) cells that carry a lysine-to-methionine substitution in histone H3 (H3K27M), but not in cells that carry either EZH2 or EED mutants that abrogate PRC2 allosteric activation, indicating that H3K27M impairs the intrinsic activity of PRC2. Our study demonstrates a PRC2 self-regulatory mechanism through its EZH1/2-mediated automethylation activity.

Indexed as

ChildEnzyme ActivationGene SilencingGliomaHistonesHumansLysineMethylationPolycomb Repressive Complex 2Protein SubunitsHistonesLysinePolycomb Repressive Complex 2Protein SubunitsautomethylationH3K27Mpediatric gliomaPolycombPRC2

Identifiers

PMID31488577
PMCPMC6771381
OpenAlexW2971693570

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.