ArticleFree radical biology & medicine2010
CpG methylation attenuates Sp1 and Sp3 binding to the human extracellular superoxide dismutase promoter and regulates its cell-specific expression.
Article in Free radical biology & medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 69 citations in OpenAlex.
- Extracellular Superoxide Dismutase in Acute Respiratory Distress Syndrome: Pathogenic Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Review
- Role of copper and SOD3-mediated extracellular redox regulation in tumor progression.Journal of clinical biochemistry and nutrition · 2024Article
- Copper in the tumor microenvironment and tumor metastasis.Journal of clinical biochemistry and nutrition · 2022Article
- SOD3 Is a Non-Mutagenic Growth Regulator Affecting Cell Migration and Proliferation Signal Transduction.Antioxidants (Basel, Switzerland) · 2021Article
- The Involvement of the Oxidative Stress Status in Cancer Pathology: A Double View on the Role of the Antioxidants.Oxidative medicine and cellular longevity · 2021Review
- DNA Methylation Inhibits the Expression of CFSH in Mud Crab.Frontiers in endocrinology · 2020Article
- The dynamic uptake and release of SOD3 from intracellular stores in macrophages modulates the inflammatory response.Redox biology · 2019Article
- Carcinogenesis and Reactive Oxygen Species Signaling: Interaction of the NADPH Oxidase NOX1-5 and Superoxide Dismutase 1-3 Signal Transduction Pathways.Antioxidants & redox signaling · 2019Review
- Extracellular superoxide dismutase and its role in cancer.Free radical biology & medicine · 2017Review
- Investigation of the role of DNA methylation in the expression of ERBB2 in human myocardium.Gene · 2017Article
- Paradoxical roles of dual oxidases in cancer biology.Free radical biology & medicine · 2017Review
- Tumor necrosis factor-α decreases EC-SOD expression through DNA methylation.Journal of clinical biochemistry and nutrition · 2017Article
- DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity.Oncotarget · 2017Article
- Exendin-4 induces extracellular-superoxide dismutase through histone H3 acetylation in human retinal endothelial cells.Journal of clinical biochemistry and nutrition · 2016Article
- ITPKA Gene Body Methylation Regulates Gene Expression and Serves as an Early Diagnostic Marker in Lung and Other Cancers.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2016Article
- CpG site methylation in CRYAA promoter affect transcription factor Sp1 binding in human lens epithelial cells.BMC ophthalmology · 2016Article
- Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Characterization of the Methylation Status of Pax7 and Myogenic Regulator Factors in Cell Myogenic Differentiation.Asian-Australasian journal of animal sciences · 2016Article
- Hepatoprotective Effects of Chinese Medicinal Herbs: A Focus on Anti-Inflammatory and Anti-Oxidative Activities.International journal of molecular sciences · 2016Review
- Exendin-4 promotes extracellular-superoxide dismutase expression in A549 cells through DNA demethylation.Journal of clinical biochemistry and nutrition · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular superoxide dismutase (EC-SOD) plays an important role in maintaining normal redox homeostasis in the lung. It is expressed at very high levels in pulmonary fibroblasts, alveolar type II epithelial cells, and smooth muscle cells. The molecular mechanisms governing this cell-specific expression of EC-SOD are mostly unknown. In our previous studies we showed that EC-SOD cell-specific expression was not attributable to differential transcriptional regulation, suggesting that other, possibly epigenetic, mechanisms are involved in regulation of its expression. In this paper, we show high levels of promoter methylation in A549 cells and correspondingly low levels of methylation in MRC5 cells. Inhibition of DNA methyltransferase activity by 5-azacytidine in A549 cells reactivated EC-SOD transcription (2.75+/-0.16-fold, P<0.001), demonstrating the importance of methylation in the repression of EC-SOD expression. Furthermore, methylation of cytosines in the promoter markedly decreased Sp1/Sp3-driven promoter activity to 30.09+/-2.85% (P<0.001) compared to unmethylated promoter. This attenuation of transcription of the promoter/reporter construct was, at least in part, attributable to the binding of the methyl-binding protein MeCP2 in the insect cells. However, no binding of MeCP2 or MBD2 protein to the EC-SOD promoter was detected in mammalian cells in vivo. We also found marked differences in the chromatin organization of the EC-SOD promoter between these two cell lines, further supporting the important role epigenetic modifications play in the regulation of EC-SOD expression.
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