ArticleNucleic acids research2015
Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Serum RNA Profile Reflects Fluid Status and Atrophic Retinal Changes in Neovascular Age-Related Macular Degeneration.International journal of molecular sciences · 2025Article
- The cytoglobin-dependent transcriptome in melanoma indicates a protective function associated with oxidative stress, inflammation and cancer-associated pathways.Scientific reports · 2024Article
- Article
- Targeting the chromatin structural changes of antitumor immunity.Journal of pharmaceutical analysis · 2024Review
- Therapeutic Effects and Molecular Mechanism of Chlorogenic Acid on Polycystic Ovarian Syndrome: Role of HIF-1alpha.Nutrients · 2023Review
- CRISPR Activator Approaches to Study Endogenous Androglobin Gene Regulation.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The effect of HIF on metabolism and immunity.Nature reviews. Nephrology · 2022Review
- Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response.Redox biology · 2022Article
- Cytoglobin Silencing Promotes Melanoma Malignancy but Sensitizes for Ferroptosis and Pyroptosis Therapy Response.Antioxidants (Basel, Switzerland) · 2022Article
- Analysis of the Hypoxic Response in a Mouse Cortical Collecting Duct-Derived Cell Line Suggests That Esrra Is Partially Involved in Hif1α-Mediated Hypoxia-Inducible Gene Expression in mCCDInternational journal of molecular sciences · 2022Article
- Article
- The roles of inducible chromatin and transcriptional memory in cellular defense system responses to redox-active pollutants.Free radical biology & medicine · 2021Review
- A reliable set of reference genes to normalize oxygen-dependent cytoglobin gene expression levels in melanoma.Scientific reports · 2021Article
- Hypoxia-Induced LIN28A mRNA Promotes the Metastasis of Colon Cancer in a Protein-Coding-Independent Manner.Frontiers in cell and developmental biology · 2021Article
- Hypoxia Response Element-Directed Expression of aFGF in Neural Stem Cells Promotes the Recovery of Spinal Cord Injury and Attenuates SCI-Induced Apoptosis.Frontiers in cell and developmental biology · 2021Article
- Hypoxic Regulation of Gene Transcription and Chromatin: Cause and Effect.International journal of molecular sciences · 2020Review
- Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis.International journal of molecular sciences · 2020Review
- Article
- Coordinated regulation of IFITM1, 2 and 3 genes by an IFN-responsive enhancer through long-range chromatin interactions.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Article
- Capture-C reveals preformed chromatin interactions between HIF-binding sites and distant promoters.EMBO reports · 2016Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
A crucial step in the cellular adaptation to oxygen deficiency is the binding of hypoxia-inducible factors (HIFs) to hypoxia response elements (HREs) of oxygen-regulated genes. Genome-wide HIF-1α/2α/β DNA-binding studies revealed that the majority of HREs reside distant to the promoter regions, but the function of these distal HREs has only been marginally studied in the genomic context. We used chromatin immunoprecipitation (ChIP), gene editing (TALEN) and chromosome conformation capture (3C) to localize and functionally characterize a 82 kb upstream HRE that solely drives oxygen-regulated expression of the newly identified HIF target gene PAG1. PAG1, a transmembrane adaptor protein involved in Src signalling, was hypoxically induced in various cell lines and mouse tissues. ChIP and reporter gene assays demonstrated that the -82 kb HRE regulates PAG1, but not an equally distant gene further upstream, by direct interaction with HIF. Ablation of the consensus HRE motif abolished the hypoxic induction of PAG1 but not general oxygen signalling. 3C assays revealed that the -82 kb HRE physically associates with the PAG1 promoter region, independent of HIF-DNA interaction. These results demonstrate a constitutive interaction between the -82 kb HRE and the PAG1 promoter, suggesting a physiologically important rapid response to hypoxia.
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Registered trials
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