ArticlePloS one2013
Structural context of disease-associated mutations and putative mechanism of autoinhibition revealed by X-ray crystallographic analysis of the EZH2-SET domain.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Structural characteristics and SARs of EZH2 inhibitors.Molecular diversity · 2026Review
- Enhancer of Zeste Homolog 2 (EZH2): From Glioblastoma Biology to Potential Epigenetic Therapy.International journal of molecular sciences · 2026Review
- In-silico assessment of phytochemical derivatives generated using CHEESE webserver for advancement of druggable candidate in pancreatic cancer therapy.In silico pharmacology · 2026Article
- The role of ASXL1, SRSF2, and EZH2 mutations in chromatin dysregulation of myelodysplastic neoplasia and acute myeloid leukemia.Leukemia · 2025Review
- Tumor-suppressive functions of protein lysine methyltransferases.Experimental & molecular medicine · 2023Review
- EZH2 in hepatocellular carcinoma: progression, immunity, and potential targeting therapies.Experimental hematology & oncology · 2023Review
- Epigenetic regulation of embryonic ectoderm development in stem cell differentiation and transformation during ontogenesis.Cell proliferation · 2023Review
- Exploring the therapeutic potential of targeting polycomb repressive complex 2 in lung cancer.Frontiers in oncology · 2023Review
- Rare diseases of epigenetic origin: Challenges and opportunities.Frontiers in genetics · 2023Review
- The transcriptional elongation factor CTR9 demarcates PRC2-mediated H3K27me3 domains by altering PRC2 subtype equilibrium.Nucleic acids research · 2022Article
- PRC2, Chromatin Regulation, and Human Disease: Insights From Molecular Structure and Function.Frontiers in oncology · 2022Review
- The molecular principles of gene regulation by Polycomb repressive complexes.Nature reviews. Molecular cell biology · 2021Review
- Polycomb Repressive Complex 2 Modulation through the Development of EZH2-EED Interaction Inhibitors and EED Binders.Journal of medicinal chemistry · 2021Review
- Cooperative DNA looping by PRC2 complexes.Nucleic acids research · 2021Article
- Polycomb Gene Silencing Mechanisms: PRC2 Chromatin Targeting, H3K27me3 'Readout', and Phase Separation-Based Compaction.Trends in genetics : TIG · 2021Review
- Allosteric regulation of histone lysine methyltransferases: from context-specific regulation to selective drugs.Biochemical Society transactions · 2021Review
- Full methylation of H3K27 by PRC2 is dispensable for initial embryoid body formation but required to maintain differentiated cell identity.Development (Cambridge, England) · 2021Article
- A Structural Perspective on Gene Repression by Polycomb Repressive Complex 2.Sub-cellular biochemistry · 2021Review
- Article
- Engaging chromatin: PRC2 structure meets function.British journal of cancer · 2020Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The enhancer-of-zeste homolog 2 (EZH2) gene product is an 87 kDa polycomb group (PcG) protein containing a C-terminal methyltransferase SET domain. EZH2, along with binding partners, i.e., EED and SUZ12, upon which it is dependent for activity forms the core of the polycomb repressive complex 2 (PRC2). PRC2 regulates gene silencing by catalyzing the methylation of histone H3 at lysine 27. Both overexpression and mutation of EZH2 are associated with the incidence and aggressiveness of various cancers. The novel crystal structure of the SET domain was determined in order to understand disease-associated EZH2 mutations and derive an explanation for its inactivity independent of complex formation. The 2.00 Å crystal structure reveals that, in its uncomplexed form, the EZH2 C-terminus folds back into the active site blocking engagement with substrate. Furthermore, the S-adenosyl-L-methionine (SAM) binding pocket observed in the crystal structure of homologous SET domains is notably absent. This suggests that a conformational change in the EZH2 SET domain, dependent upon complex formation, must take place for cofactor and substrate binding activities to be recapitulated. In addition, the data provide a structural context for clinically significant mutations found in the EZH2 SET domain.
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