ArticleMolecular and cellular biology2012
Dynamic change of chromatin conformation in response to hypoxia enhances the expression of GLUT3 (SLC2A3) by cooperative interaction of hypoxia-inducible factor 1 and KDM3A.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 1 of them a synthesis that pooled it.
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Who cites it
148 citing papers in PubMed, 1 synthesis or guideline pooled it, 251 citations in OpenAlex.
- Genetics of breast cancer bone metastasis: a sequential multistep pattern.Clinical & experimental metastasis · 2014Pooled it
- Iron Deficiency Impairs Mitochondrial Energetics and Early Axonal Growth and Branching in Developing Hippocampal Neurons.The Journal of nutrition · 2026Article
- Genomic characterization and pathogenicity validation of Mycoplasma ovipneumoniae strains from diseased sheep: insights into potential pathogenic mechanisms of GSWW364.Veterinary research · 2026Article
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- DDX21 Promotes Breast Cancer Growth and Metastasis via Stimulating RNAPII Elongation During Hypoxia.MedComm · 2026Article
- Tanshinone IIA alleviates chronic endometritis via DRAK2 inhibition to restore mitochondrial function and suppress KDM3A-SLC2A3-driven NETs formation.Journal of molecular histology · 2026Article
- Long non-coding RNA LINC00607 epigenetically regulates endothelial TSPAN18 to promote hypoxia-induced thromboinflammation.The Journal of biological chemistry · 2026Article
- RTK AXL and its Isoforms: Regulation and Implications in Cancer.Current medicinal chemistry · 2026Review
- Epigenetic memories induced by hypoxia in AKI-to-CKD transition.Clinical and experimental nephrology · 2025Review
- Hypoxic BMSCs accelerate femur fracture healing via the METTL3/SLC2A3 m6A-glycolysis axis.Journal of translational medicine · 2025Article
- Neural Responses to Hypoxic Injury in a Vascularized Cerebral Organoid Model.Neuroscience bulletin · 2025Article
- Tfcp2l1 as a central integrator of hypoxia, dedifferentiation, and tumor progression.Journal of experimental & clinical cancer research : CR · 2025Review
- Article
- A Narrative Review on the Effect of Valproic Acid on the Placenta.Birth defects research · 2025Review
- Growth factor and hypoxia-inducible factor alpha content in the retina of male Wistar rats in experimental diabetic retinopathy and the effect of cellular protein kinase blockade.Frontiers in endocrinology · 2025Article
- Pemafibrate Induces a Low Level of PPARα Agonist-Stimulated mRNA Expression of ANGPTL4 in ARPE19 Cell.Bioengineering (Basel, Switzerland) · 2024Article
- Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss.Journal of clinical medicine · 2024Article
- miR-449a: A Promising Biomarker and Therapeutic Target in Cancer and Other Diseases.Cell biochemistry and biophysics · 2024Review
- Systematic single-cell analysis reveals dynamic control of transposable element activity orchestrating the endothelial-to-hematopoietic transition.BMC biology · 2024Article
- GIP attenuates neuronal oxidative stress by regulating glucose uptake in spinal cord injury of rat.CNS neuroscience & therapeutics · 2024Article
88 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor 1 (HIF1) is a master regulator of adaptive gene expression under hypoxia. However, a role for HIF1 in the epigenetic regulation remains unknown. Genome-wide analysis of HIF1 binding sites (chromatin immunoprecipitation [ChIP] with deep sequencing) of endothelial cells clarified that HIF1 mainly binds to the intergenic regions distal from transcriptional starting sites under both normoxia and hypoxia. Next, we examined the temporal profile of gene expression under hypoxic conditions by using DNA microarrays. We clarified that early hypoxia-responsive genes are functionally associated with glycolysis, including GLUT3 (SLC2A3). Acetylated lysine 27 of histone 3 covered the HIF1 binding sites, and HIF1 functioned as an enhancer of SLC2A3 by interaction with lysine (K)-specific demethylase 3A (KDM3A). Knockdown of HIF1α and KDM3A showed that glycolytic genes are regulated by both HIF1 and KDM3A and respond to hypoxia in a manner independent of cell type specificity. We elucidated that both the chromatin conformational structure and histone modification change under hypoxic conditions and enhance the expression of SLC2A3 based on the combined results of chromatin conformation capture (3C) and ChIP assays. KDM3A is recruited to the SLC2A3 locus in an HIF1-dependent manner and demethylates H3K9me2 so as to upregulate its expression. These findings provide novel insights into the interaction between HIF1 and KDM3A and also the epigenetic regulation of HIF1.
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