ArticleCellular and molecular life sciences : CMLS2020
A long hypoxia-inducible factor 3 isoform 2 is a transcription activator that regulates erythropoietin.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 61 citations in OpenAlex.
- Mitochondrial Transplantation Rejuvenates Aging Heart by Restoring Mitophagy Flux via the HIF-3α-BNIP3 Axis.Aging cell · 2026Article
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- An Activity-Dependent NEPAS-PTX3 Axis Links Neurovascular and Myelin Deficits to Cognitive Impairment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Nuclear translocation of SLC25A10 isoform 3 promotes chemoresistance in HCC cells via CEBPB/BCL2A1 signaling.Cell death & disease · 2026Article
- Theranostic Nanoparticles in Prostate Cancer: Disrupting Hypoxia-Induced Glycolysis by Targeting Hypoxia-Inducible Factor-1 Alpha and Downstream Metabolites.Cancer medicine · 2026Review
- HIF-mediated hierarchical hypoxic adaptation, a novel paradigm in heart failure pathogenesis: is there a role for targeted therapies?Frontiers in pharmacology · 2026Review
- Molecular mechanism of the crosstalk between glucocorticoid receptor (GR) and hypoxia-inducible factor 3α (HIF-3α) pathways.Marine life science & technology · 2025Article
- Extracellular DNA, hyaluronic acid, HIF pathways, and LncRNAs as predictive biomarkers of severe COVID-19.Virology journal · 2025Review
- Epitranscriptomic regulation of HIF-1: bidirectional regulatory pathways.Molecular medicine (Cambridge, Mass.) · 2025Review
- Hypoxia Inducible Factor-2α (HIF-2α) Pathway Inhibitors.Journal of kidney cancer and VHL · 2025Review
- Investigating the neuroprotective effect of heparin in improving mitochondrial function in rats with cardiac arrest cardiopulmonary resuscitation based on transcriptome sequencing.Frontiers in medicine · 2025Article
- siRNA silencing and hypoxia challenge indicate that the function of common carp (Cyprinus carpio) hif-1αb genes are tightly linked to hif-1αa and hif-3α genes.BMC genomics · 2024Article
- Influence of Hypoxia on the Airway Epithelium.Physiological research · 2024Review
- Review
- Article
- Hypoxia inducible factor (HIF) 3α prevents COPD by inhibiting alveolar epithelial cell ferroptosis via the HIF-3α-GPx4 axis.Theranostics · 2024Article
- Screening of functional genes for hypoxia adaptation in Tibetan pigs by combined genome resequencing and transcriptome analysis.Frontiers in veterinary science · 2024Article
- Expression of HIF‑α and their association with clinicopathological parameters in clinical renal cell carcinoma.Upsala journal of medical sciences · 2024Article
- Sensing the oxygen and temperature in the adipose tissues - who's sensing what?Experimental & molecular medicine · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Hypoxia-inducible factor (HIF), an αβ dimer, is the master regulator of oxygen homeostasis with hundreds of hypoxia-inducible target genes. Three HIF isoforms differing in the oxygen-sensitive α subunit exist in vertebrates. While HIF-1 and HIF-2 are known transcription activators, HIF-3 has been considered a negative regulator of the hypoxia response pathway. However, the human HIF3A mRNA is subject to complex alternative splicing. It was recently shown that the long HIF-3α variants can form αβ dimers that possess transactivation capacity. Here, we show that overexpression of the long HIF-3α2 variant induces the expression of a subset of genes, including the erythropoietin (EPO) gene, while simultaneous downregulation of all HIF-3α variants by siRNA targeting a shared HIF3A region leads to downregulation of EPO and additional genes. EPO mRNA and protein levels correlated with HIF3A silencing and HIF-3α2 overexpression. Chromatin immunoprecipitation analyses showed that HIF-3α2 binding associated with canonical hypoxia response elements in the promoter regions of EPO. Luciferase reporter assays showed that the identified HIF-3α2 chromatin-binding regions were sufficient to promote transcription by all three HIF-α isoforms. Based on these data, HIF-3α2 is a transcription activator that directly regulates EPO expression.
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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.