ArticleNucleic acids research2018
Methylation of hypoxia-inducible factor (HIF)-1α by G9a/GLP inhibits HIF-1 transcriptional activity and cell migration.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 123 citations in OpenAlex.
- DDX21 Promotes Breast Cancer Growth and Metastasis via Stimulating RNAPII Elongation During Hypoxia.MedComm · 2026Article
- Mimicking mammalian hibernation to lock cancer cells in safe quiescence.Discover oncology · 2026Article
- Transcriptional condensates enrich phosphorylated PRMT2 to stimulate H3R8me2a deposition and hypoxic response in glioblastoma.Science China. Life sciences · 2026Article
- miR-652-5p promoter hypermethylation enhances glioblastoma malignancy through the SDC1/TGFβ2/pERBB4 complex via HIF2α-mediated regulation under hypoxia.Cancer cell international · 2025Article
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- Neuron-derived neurotrophic factor and its biological functions: a review study.Molecular biology reports · 2025Review
- The novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma.Respiratory research · 2025Article
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects.Cellular and molecular life sciences : CMLS · 2025Review
- Solute carrier family 6 member 3 promotes the development of clear cell renal cell carcinoma by enhancing glycolysis and inhibiting ferroptosis.CytoJournal · 2025Article
- The epigenetic mechanisms involved in the treatment resistance of glioblastoma.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.PLoS biology · 2024Article
- Histone lysine methylation modifiers controlled by protein stability.Experimental & molecular medicine · 2024Review
- Citrullination modulation stabilizes HIF-1α to promote tumour progression.Nature communications · 2024Article
- Histone H3K9 Methylation Features under Hypoxic Conditions after the HIF1A Knockdown in Mesenchymal Stromal Cells In Vitro.Bulletin of experimental biology and medicine · 2024Article
- HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma.Cell death discovery · 2024Article
- Dual targeting of KDM1A and antioxidants is an effective anticancer strategy.bioRxiv : the preprint server for biology · 2024Article
- Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review.Cancers · 2024Review
- Strategies that regulate LSD1 for novel therapeutics.Acta pharmaceutica Sinica. B · 2024Review
- IFI16 Is Indispensable for Promoting HIF-1α-Mediated APOL1 Expression in Human Podocytes under Hypoxic Conditions.International journal of molecular sciences · 2024Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator in response to hypoxia and its transcriptional activity is crucial for cancer cell mobility. Here we present evidence for a novel epigenetic mechanism that regulates HIF-1 transcriptional activity and HIF-1-dependent migration of glioblastoma cells. The lysine methyltransferases G9a and GLP directly bound to the α subunit of HIF-1 (HIF-1α) and catalyzed mono- and di-methylation of HIF-1α at lysine (K) 674 in vitro and in vivo. K674 methylation suppressed HIF-1 transcriptional activity and expression of its downstream target genes PTGS1, NDNF, SLC6A3, and Linc01132 in human glioblastoma U251MG cells. Inhibition of HIF-1 by K674 methylation is due to reduced HIF-1α transactivation domain function but not increased HIF-1α protein degradation or impaired binding of HIF-1 to hypoxia response elements. K674 methylation significantly decreased HIF-1-dependent migration of U251MG cells under hypoxia. Importantly, we found that G9a was downregulated by hypoxia in glioblastoma, which was inversely correlated with PTGS1 expression and survival of patients with glioblastoma. Therefore, our findings uncover a hypoxia-induced negative feedback mechanism that maintains high activity of HIF-1 and cell mobility in human glioblastoma.
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