鉴定与动脉粥样硬化相关的人 12/15-脂氧合酶启动子变异体的特征，发现中间丝蛋白作为启动子结合蛋白。
Characterization of a human 12/15-lipoxygenase promoter variant associated with atherosclerosis identifies vimentin as a promoter binding protein.
机构信息
Research Center for Human Genetics, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
出版信息
PLoS One. 2012;7(8):e42417. doi: 10.1371/journal.pone.0042417. Epub 2012 Aug 7.
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.
背景
人类 12/15 脂氧合酶（ALOX15）的序列变异与动脉粥样硬化疾病有关。我们对先前与颈动脉斑块负担相关的 ALOX15 启动子多态性 rs2255888 进行了功能表征。
方法/主要发现：我们证明了细胞骨架蛋白波形蛋白在体外和体内特异性结合 ALOX15 启动子。我们通过在两种细胞系中的荧光素酶报告基因检测显示，携带 rs2255888 交替等位基因的两个启动子单倍型在启动子活性方面存在显著差异。通过电泳迁移率变动分析和生物物理分析，还分别检测到在多态性启动子序列中体外波形蛋白结合和形成 DNA 二级结构的差异。我们显示了波形蛋白对 ALOX15 蛋白的调节。
结论/意义：这项研究表明，波形蛋白结合 ALOX15 启动子并调节其启动子活性和蛋白表达。导致 DNA 构象变化和波形蛋白与启动子结合的序列变异可能与 ALOX15 基因调节有关。
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