ArticleProceedings of the National Academy of Sciences of the United States of America2014
O-GlcNAcylation regulates EZH2 protein stability and function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 227 citations in OpenAlex.
- Preclinical assessment of GNEFuture science OA · 2026Article
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- O-GlcNAcylation regulates PPAR-driven metabolic programming in intestinal stem cells.bioRxiv : the preprint server for biology · 2026Article
- Maternal O-GlcNAc Transferase Is Required for the Asymmetry of Epigenetic Modifications in Mouse Zygotes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Human O-GlcNAcase catalytic-stalk dimer anchors flexible histone binding domains.Communications chemistry · 2025Article
- The plant epigenome governed by nutrients and metabolism.Current opinion in plant biology · 2025Review
- Sublytic Activity of a Pore-Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour-Affiliated Protein Expression.Journal of extracellular vesicles · 2025Article
- Upregulation of OGT-mediated EZH2 O-GlcNAcylation Promotes Human Umbilical Vein Endothelial Cell Proliferation, Invasion, Migration, and Tube Formation in Gestational Diabetes Mellitus.Cell biochemistry and biophysics · 2025Article
- S-nitrosylation of EZH2 alters PRC2 assembly, methyltransferase activity, and EZH2 stability to maintain endothelial homeostasis.Nature communications · 2025Article
- HumanResearch square · 2025Article
- Functional genomic profiling of O-GlcNAc reveals its context-specific interplay with RNA polymerase II.Genome biology · 2025Article
- Structural glycobiology - from enzymes to organelles.Biochemical Society transactions · 2025Review
- Coupling of glucose metabolism with mitophagy via O-GlcNAcylation of PINK1.International journal of biological sciences · 2025Article
- Tissue block-resolved developmental transcriptomic atlas of human fetal brainstem reveals gene modules with implications for neurological disorders.Frontiers in cell and developmental biology · 2025Article
- Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential.Molecules (Basel, Switzerland) · 2024Review
- Cardiovascular Disease and miRNAs: Possible Oxidative Stress-Regulating Roles of miRNAs.Antioxidants (Basel, Switzerland) · 2024Review
- O-GlcNAc regulates anti-fibrotic genes in lung fibroblasts through EZH2.Journal of cellular and molecular medicine · 2024Article
- O-GlcNAcylation mediates HActa pharmacologica Sinica · 2024Article
- Paternal DDT exposure induces sex-specific programming of fetal growth, placenta development and offspring's health phenotypes in a mouse model.Scientific reports · 2024Article
- O-GlcNAcylation: the sweet side of epigenetics.Epigenetics & chromatin · 2023Review
89 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. OGT participates in transcriptional and epigenetic regulation, and dysregulation of OGT has been implicated in diseases such as cancer. However, the underlying mechanism is largely unknown. Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). H3K27me3 is one of the most important histone modifications to mark the transcriptionally silenced chromatin. We found that the level of H3K27me3, but not other H3 methylation products, was greatly reduced upon OGT depletion. OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. Furthermore, the interaction of OGT and EZH2/PRC2 was detected by coimmunoprecipitation and cosedimentation experiments. Importantly, we identified that serine 75 is the site for EZH2 O-GlcNAcylation, and the EZH2 mutant S75A exhibited reduction in stability. Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT-EZH2 axis. Together these results indicate that OGT-mediated O-GlcNAcylation at S75 stabilizes EZH2 and hence facilitates the formation of H3K27me3. The study not only uncovers a functional posttranslational modification of EZH2 but also reveals a unique epigenetic role of OGT in regulating histone methylation.
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