ArticleTranscription
The endoglycosidase heparanase enters the nucleus of T lymphocytes and modulates H3 methylation at actively transcribed genes via the interplay with key chromatin modifying enzymes.
Article in Transcription. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma.Cells · 2023Article
- Heparanase Modulates Chromatin Accessibility.Cells · 2023Article
- Heparanase Increases Podocyte Survival and Autophagic Flux after Adriamycin-Induced Injury.International journal of molecular sciences · 2022Article
- Non-enzymatic heparanase enhances gastric tumor proliferation via TFEB-dependent autophagy.Oncogenesis · 2022Article
- Upregulation of ERK-EGR1-heparanase axis by HDAC inhibitors provides targets for rational therapeutic intervention in synovial sarcoma.Journal of experimental & clinical cancer research : CR · 2021Article
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- Disruption of innate defense responses by endoglycosidase HPSE promotes cell survival.JCI insight · 2021Article
- Dissociation of DNA damage sensing by endoglycosidase HPSE.iScience · 2021Article
- Heparanase-enhanced Shedding of Syndecan-1 and Its Role in Driving Disease Pathogenesis and Progression.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- New classes of potent heparanase inhibitors from ligand-based virtual screening.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- Significance of host heparanase in promoting tumor growth and metastasis.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity.Molecules (Basel, Switzerland) · 2020Review
- Nuclear Heparanase Regulates Chromatin Remodeling, Gene Expression and PTEN Tumor Suppressor Function.Cells · 2020Article
- The Challenge of Modulating Heparan Sulfate Turnover by Multitarget Heparin Derivatives.Molecules (Basel, Switzerland) · 2020Review
- Heparanase and Chemotherapy Synergize to Drive Macrophage Activation and Enhance Tumor Growth.Cancer research · 2020Article
- Heparanase: A Dynamic Promoter of Myeloma Progression.Advances in experimental medicine and biology · 2020Review
- Forty Years of Basic and Translational Heparanase Research.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The methylation of histones is a fundamental epigenetic process regulating gene expression programs in mammalian cells. Dysregulated patterns of histone methylation are directly implicated in malignant transformation. Here, we report the unexpected finding that the invasive extracellular matrix degrading endoglycosidase heparanase enters the nucleus of activated human T lymphocytes and regulates the transcription of a cohort of inducible immune response genes by controlling histone H3 methylation patterns. It was found that nuclear heparanase preferentially associates with euchromatin. Genome-wide ChIP-on-chip analyses showed that heparanase is recruited to both the promoter and transcribed regions of a distinct cohort of transcriptionally active genes. Knockdown and overexpression of the heparanase gene also showed that chromatin-bound heparanase is a prerequisite for the transcription of a subset of inducible immune response genes in activated T cells. Furthermore, the actions of heparanase seem to influence gene transcription by associating with the demethylase LSD1, preventing recruitment of the methylase MLL and thereby modifying histone H3 methylation patterns. These data indicate that heparanase belongs to an emerging class of proteins that play an important role in regulating transcription in addition to their well-recognized extra-nuclear functions.
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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.