G-quadruplexes in the BAP1 promoter positively regulate its expression
G-quadruplexes in the BAP1 promoter positively regulate its expression
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BAP1 启动子中的 G 四链体正向调节其表达
DOI：
10.1016/j.yexcr.2018.05.016
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发表时间：
2018-08-01
影响因子：
3.7
通讯作者：
Sui, Guangchao
中科院分区：
文献类型：
--
作者：
Li, Yingzhou;Zhang, Xiao;Sui, Guangchao
越来越多的证据表明BAP1在肿瘤发生中起关键作用，但调节BAP1基因表达的机制仍未被探索。在本报告中，我们发现BAP1启动子在其负链上含有多个g -束，具有形成g -四重体（G4）结构的高潜力。在圆二色性研究中，在BAP1转录起始位点上游这些富g区域内合成的寡核苷酸在G4结构的特定波长上表现出摩尔椭圆性。通过天然聚丙烯酰胺凝胶电泳对这些寡核苷酸进行分析，发现形成了多种类型的G4结构。在报告基因分析中，预测的G4结构的突变或缺失会降低BAP1启动子的活性。此外，DNA解旋酶CHD2和CHD7可能通过解绕其G4结构来降低BAP1启动子活性。
Accumulating evidence suggests a key role of BAP1 in oncogenesis, but mechanisms regulating BAP1 gene expression remain unexplored. In this report, we revealed that the BAP1 promoter contains multiple G-tracts in its negative strand with high potential of forming G-quadruplex (G4) structures. In circular dichroism studies, synthesized oligonucleotides within these G-rich regions upstream the BAP1 transcription start site showed molar ellipticity at specific wavelengths characteristic of G4 structures. Analyses of these oligonucleotides by native polyacrylamide gel electrophoresis revealed formation of multiple types of G4 structures. In reporter assays, mutations or deletion of predicted G4 structures reduced BAP1 promoter activity. Additionally, DNA helicases CHD2 and CHD7 could reduce BAP1 promoter activity, likely through unwinding its G4 structures.