ArticleEMBO reports2017
A non-canonical function of Ezh2 preserves immune homeostasis.
Article in EMBO reports, 2017. 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, 85 citations in OpenAlex.
- Old versus new: upstream and downstream of promyelocytic leukemia zinc finger protein.Cancer gene therapy · 2025Review
- Mechanisms and Therapeutic Implications of EZH2 in Nasal Diseases.Clinical reviews in allergy & immunology · 2025Review
- Antisense-mediated exon skipping targeting EZH2 suppresses tumor growth in a xenograft mouse model of hepatocellular carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- MAIT cells: Conserved watchers on the wall.The Journal of experimental medicine · 2025Review
- Exploring oncogenic roles and clinical significance of EZH2: focus on non-canonical activities.Therapeutic advances in medical oncology · 2025Review
- Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential.Molecules (Basel, Switzerland) · 2024Review
- A conserved transcriptional program for MAIT cells across mammalian evolution.The Journal of experimental medicine · 2024Article
- Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways.The Journal of clinical investigation · 2024Article
- Eed-dependent histone modification orchestrates the iNKT cell developmental program alleviating liver injury.Frontiers in immunology · 2024Article
- Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC.Nature communications · 2023Article
- Lsd1 safeguards T-cell development via suppressing endogenous retroelements and interferon responses.Life science alliance · 2023Article
- Non-canonical functions of EZH2 in cancer.Frontiers in oncology · 2023Review
- Transient Polycomb activity represses developmental genes in growing oocytes.Clinical epigenetics · 2022Article
- PRC2-Mediated Epigenetic Suppression of Type I IFN-STAT2 Signaling Impairs Antitumor Immunity in Luminal Breast Cancer.Cancer research · 2022Article
- Progranulin regulates the development and function of NKT2 cells through EZH2 and PLZF.Cell death and differentiation · 2022Article
- EZH2 Inhibition and Cisplatin as a Combination Anticancer Therapy: An Overview of Preclinical Studies.Cancers · 2022Review
- Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes.International journal of molecular sciences · 2022Article
- EZH2 engages TGFβ signaling to promote breast cancer bone metastasis via integrin β1-FAK activation.Nature communications · 2022Article
- Link between the EZH2 noncanonical pathway and microtubule organization center polarization during early T lymphopoiesis.Scientific reports · 2022Article
- EZH2 Promotes T Follicular Helper Cell Differentiation Through Enhancing STAT3 Phosphorylation in Patients With Primary Sjögren's Syndrome.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3. In contrast, removal of Suz12 or Eed destabilizes canonical PRC2 function and ablates NKT cell development completely. We further show that Ezh2 directly methylates the NKT cell lineage defining transcription factor PLZF, leading to its ubiquitination and subsequent degradation. Sustained PLZF expression in Ezh2-deficient mice is associated with the expansion of a subset of NKT cells that cause immune perturbation. Taken together, we have identified a chromatin-independent function of Ezh2 that impacts on the development of the immune system.
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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.