Evidence of the formation of G-quadruplex structures in the promoter region of the human vascular endothelial growth factor gene.
Evidence of the formation of G-quadruplex structures in the promoter region of the human vascular endothelial growth factor gene.
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DOI：
10.1093/nar/gkq926
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发表时间：
2011-03
影响因子：
14.9
通讯作者：
Shin YJ
中科院分区：
文献类型：
--
作者：
Sun D;Guo K;Shin YJ
人血管内皮生长因子（VEGF）基因的多嘌呤/多嘧啶（pPu/pPy）道被认为是结构动态的，并有可能采用非B DNA结构。在本研究中，我们进一步提供证据的存在下，在这道内的G-四链体结构在体外和体内使用硫酸二甲酯（DMS）足迹技术和核仁素作为结构探针特异性识别G-四链体结构。我们观察到，在体外和体内足迹实验中，与侧翼区域的其他鸟嘌呤残基相比，该道内的鸟嘌呤残基对DMS的整体反应性显著降低。我们还证明，核仁素，这是已知的G-四链体结构结合，能够特异性地结合到负超螺旋DNA中该区域的G-丰富的序列。我们的染色质免疫沉淀分析进一步揭示了结合核仁素的VEGF基因的启动子区域在体内。两者合计，我们的研究结果是在我们的假设，如G-四链体，可以形成在超螺旋双链体DNA和DNA在染色质中在体内的生理条件下形成类似的单链DNA模板中的二级DNA结构。
The polypurine/polypyrimidine (pPu/pPy) tract of the human vascular endothelial growth factor (VEGF) gene is proposed to be structurally dynamic and to have potential to adopt non-B DNA structures. In the present study, we further provide evidence for the existence of the G-quadruplex structure within this tract both in vitro and in vivo using the dimethyl sulfate (DMS) footprinting technique and nucleolin as a structural probe specifically recognizing G-quadruplex structures. We observed that the overall reactivity of the guanine residues within this tract toward DMS was significantly reduced compared with other guanine residues of the flanking regions in both in vitro and in vivo footprinting experiments. We also demonstrated that nucleolin, which is known to bind to G-quadruplex structures, is able to bind specifically to the G-rich sequence of this region in negatively supercoiled DNA. Our chromatin immunoprecipitation analysis further revealed binding of nucleolin to the promoter region of the VEGF gene in vivo. Taken together, our results are in agreement with our hypothesis that secondary DNA structures, such as G-quadruplexes, can be formed in supercoiled duplex DNA and DNA in chromatin in vivo under physiological conditions similar to those formed in single-stranded DNA templates.
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