ArticleOncotarget2017
The JAZF1-SUZ12 fusion protein disrupts PRC2 complexes and impairs chromatin repression during human endometrial stromal tumorogenesis.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 64 citations in OpenAlex.
- Cancer-associated fusion transcripts: mechanisms, functional roles, and clinical implications.Clinical and experimental medicine · 2026Review
- From Epigenetic Dysregulation to Therapeutic Reprogramming in Endometrial Cancer: A State-Response Framework for Treatment Resistance.International journal of molecular sciences · 2026Review
- CTNNB1 mutation represents a recurrent driver molecular alteration in a subset of endometrial stromal tumors.Virchows Archiv : an international journal of pathology · 2026Article
- Case Report: Clinicopathological features and outcomes of superficial cervicovaginal myofibroblastoma: analysis of two cases and a review of the literature.Frontiers in oncology · 2026Article
- The Evolving Molecular Landscape of Uterine Mesenchymal Tumors: Diagnostic and Therapeutic Implications.Cancers · 2025Review
- Uterine Stroma-Derived Tumors and the Extracellular Matrix: A Comparative Review of Benign and Malignant Pathologies.Cancers · 2025Review
- Metastatic endometrial stromal sarcoma with sex cord and neuroendocrine differentiation harboring a complex gene fusion.Diagnostic pathology · 2025Article
- H3K27me3-mediated epigenetic regulation in pluripotency maintenance and lineage differentiation.Cell insight · 2024Review
- Uterine Mesenchymal Tumors: Updates on Pathology, Molecular Landscape, and Therapeutics.Medicina (Kaunas, Lithuania) · 2024Review
- Targeting EED as a key PRC2 complex mediator toward novel epigenetic therapeutics.Drug discovery today · 2024Review
- Expanding the molecular spectrum of gene fusions in endometrial stromal sarcoma: Novel subunits of the chromatin remodeling complexes PRC2 and NuA4/TIP60 as alternative fusion partners.Genes, chromosomes & cancer · 2023Article
- JAZF1: A Metabolic Regulator of Sensitivity to a Polyamine-Targeted Therapy.Molecular cancer research : MCR · 2023Article
- Polycomb Repressive Complex 2 in Oncology.Cancer treatment and research · 2023Article
- TAZ/YAP fusion proteins: mechanistic insights and therapeutic opportunities.Trends in cancer · 2022Review
- Complex Elucidation of Cells-of-Origin in Pediatric Soft Tissue Sarcoma: From Concepts to Real Life, Hide-and-Seek through Epigenetic and Transcriptional Reprogramming.International journal of molecular sciences · 2022Review
- Recurrent chromosomal translocations in sarcomas create a megacomplex that mislocalizes NuA4/TIP60 to Polycomb target loci.Genes & development · 2022Article
- JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation.Cell reports · 2022Article
- Systematic Discovery of FBXW7-Binding Phosphodegrons Highlights Mitogen-Activated Protein Kinases as Important Regulators of Intracellular Protein Levels.International journal of molecular sciences · 2022Article
- Low-grade endometrial stromal sarcoma-like tumors in male with JAZF1 gene fusions.Genes, chromosomes & cancer · 2022Article
- PRC2, Chromatin Regulation, and Human Disease: Insights From Molecular Structure and Function.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The Polycomb repressive complex 2 (PRC2), which contains three core proteins EZH2, EED and SUZ12, controls chromatin compaction and transcription repression through trimethylation of lysine 27 on histone 3. The (7;17)(p15;q21) chromosomal translocation present in most cases of endometrial stromal sarcomas (ESSs) results in the in-frame fusion of the JAZF1 and SUZ12 genes. We have investigated whether and how the fusion protein JAZF1-SUZ12 functionally alters PRC2. We found that the fusion protein exists at high levels in ESS containing the t(7;17). Co-transient transfection assay indicated JAZF1-SUZ12 destabilized PRC2 components EZH2 and EED, resulting in decreased histone methyl transferase (HMT) activity, which was confirmed by in vitro studies using reconstituted PRC2 and nucleosome array substrates. We also demonstrated the PRC2 containing the fusion protein decreased the binding affinity to target chromatin loci. In addition, we found that trimethylation of H3K27 was decreased in ESS samples with the t(7;17), but there was no detectable change in H3K9 in these tissues. Moreover, re-expression of SUZ12 in Suz12 (-/-) ES cells rescued the neuronal differentiation while the fusion protein failed to restore this function and enhanced cell proliferation. In summary, our studies reveal that JAZF1-SUZ12 fusion protein disrupts the PRC2 complex, abolishes HMT activity and subsequently activates chromatin/genes normally repressed by PRC2. Such dyesfunction of PRC2 inhibits normal neural differentiation of ES cell and increases cell proliferation. Related changes induced by the JAZF-SUZ12 protein in endometrial stromal cells may explain the oncogenic effect of the t(7;17) in ESS.
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Registered trials
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.