探索 her2 原癌基因启动子中的 G-四链体结构及其识别与其转录调控。
Exploration of the Structure and Recognition of a G-quadruplex in the her2 Proto-oncogene Promoter and Its Transcriptional Regulation.
机构信息
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China.
出版信息
Sci Rep. 2019 Mar 8;9(1):3966. doi: 10.1038/s41598-019-39941-5.
G-quadruplexes in oncogene promoters provide putative targets for transcriptional regulation. The structure of a putative G-quadruplex sequence (S1: GGAGAAGGAGGAGGTGGAGGAGGAGGG) in potassium solution in the her2 promoter has been resolved mainly through nuclear magnetic resonance (NMR) spectroscopy. By application of various NMR spectra, we proved the formation of a four-layer G-quadruplex composing of two G-tetrads and two G/A-mixed planes with a four-residues loop (A3-G4-A5-A6). Further evidence from a luciferase reporter assay, Q-RT-PCR and Western blotting indicates that S1 G-quadruplex formation can repress her2 promoter activity, and a selected G-quadruplex ligand cβ can enhance the repression by down regulating her2 transcription and expression. These findings provide a G-quadruplex target and perspective implications in her2 transcriptional regulation.
原癌基因启动子中的 G-四链体为转录调控提供了潜在的靶标。通过核磁共振（NMR）光谱解析，我们确定了 HER2 启动子中一种假定的 G-四链体序列（S1：GGAGAAGGAGGAGGTGGAGGAGGAGGG）在钾溶液中的结构。通过应用各种 NMR 谱，我们证明了由两个 G-四联体和两个 G/A-混合平面以及一个四残基环（A3-G4-A5-A6）组成的四层 G-四链体的形成。来自荧光素酶报告基因检测、Q-RT-PCR 和 Western blot 的进一步证据表明，S1 G-四链体的形成可以抑制 HER2 启动子活性，而选择的 G-四链体配体 cβ 可以通过下调 HER2 转录和表达来增强抑制作用。这些发现为 HER2 转录调控中的 G-四链体靶标和观点提供了依据。
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