Characterization of a Human 12/15-Lipoxygenase Promoter Variant Associated with Atherosclerosis Identifies Vimentin as a Promoter Binding Protein
| Autor: | Kurtis M. Anderson, Myriam Fornage, David H. Hawke, Susmita Samanta, David G. Gorenstein, Sean Moran |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Oligonucleotides
lcsh:Medicine Gene Expression Vimentin Plasma protein binding Cardiovascular Biochemistry Lipoxygenase Mice Nucleic Acids Molecular Cell Biology Arachidonate 15-Lipoxygenase lcsh:Science Luciferases Promoter Regions Genetic Peptide sequence Multidisciplinary Enzymes ALOX15 MCF-7 Cells Medicine Research Article Protein Binding DNA Complementary Molecular Sequence Data Biology Transfection Polymorphism Single Nucleotide Enzyme Regulation DNA-binding proteins Animals Humans Luciferase Electrophoretic mobility shift assay Genetic Predisposition to Disease Amino Acid Sequence Base Sequence Binding protein lcsh:R Proteins DNA Atherosclerosis Molecular biology Cytoskeletal proteins Haplotypes biology.protein NIH 3T3 Cells Nucleic Acid Conformation lcsh:Q Salts |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 8, p e42417 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Background Sequence variation in the human 12/15 lipoxygenase (ALOX15) has been associated with atherosclerotic disease. We functionally characterized an ALOX15 promoter polymorphism, rs2255888, previously associated with carotid plaque burden. Methodology/Principal Findings We demonstrate specific in vitro and in vivo binding of the cytoskeletal protein, vimentin, to the ALOX15 promoter. We show that the two promoter haplotypes carrying alternate alleles at rs2255888 exhibit significant differences in promoter activity by luciferase reporter assay in two cell lines. Differences in in-vitro vimentin-binding to and formation of DNA secondary structures in the polymorphic promoter sequence are also detected by electrophoretic mobility shift assay and biophysical analysis, respectively. We show regulation of ALOX15 protein by vimentin. Conclusions/Significance This study suggests that vimentin binds the ALOX15 promoter and regulates its promoter activity and protein expression. Sequence variation that results in changes in DNA conformation and vimentin binding to the promoter may be relevant to ALOX15 gene regulation. |
| Databáze: | OpenAIRE |
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