Evidence for the presence of a guanine quadruplex forming region within a polypurine tract of the hypoxia inducible factor 1α promoter
Evidence for the presence of a guanine quadruplex forming region within a polypurine tract of the hypoxia inducible factor 1α promoter
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DOI：
10.1021/bi051618u
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发表时间：
2005-12-13
期刊：
影响因子：
2.9
通讯作者：
Ebbinghaus, SW
中科院分区：
文献类型：
--
作者：
De Armond, R;Wood, S;Ebbinghaus, SW
缺氧诱导因子1 α（HIF-1 α）基因的启动子有一个聚嘌呤/聚嘧啶区（-65到-85）与几个假定的转录因子结合位点重叠或相邻，我们发现该区域的突变减少了基础HIF-1 α的表达。通过电泳迁移率变动、化学探针、圆二色性和DNA聚合酶阻滞试验分析了代表HIF-1 α启动子这一区域的寡核苷酸。发现富含鸟嘌呤的链在钾的存在下形成平行的单分子四链体，所述钾通过两种已知的四链体结合化合物（阳离子卟啉TmPyP 4和天然产物端粒抑制素）进一步稳定，而TmPyP 2（TmPyP 4的位置异构体）不稳定四链体的形成。这些数据表明，一个四链体结构可能形成在一个区域的HIF-1 α启动子，调节基础HIF-1 α的表达。
The promoter of the hypoxia inducible factor 1 alpha (HIF-1 alpha) gene has a polvpurine/polypyrimidine tract (-65 to -85) overlapping or adjacent to several putative transcription facto;binding sites, and we found that mutagenesis of this region diminished basal HIF-1 alpha expression. Oligonucleotides representing this region of the HIF-1 alpha promoter were analyzed by electrophoretic mobility shift, chemical probing, circular dichroism, and DNA polymerase arrest assays. The guanine-rich strand was found to form a parallel, unimolecular quadruplex in the presence of potassium that was further stabilized by two known quadruplex binding compounds, the cationic porphyrin TmPyP4 and the natural product telomestatin, while TmPyP2, a positional isomer of TmPyP4, did not stabilize quadruplex formation. These data suggest that a quadruplex structure may form in a region of the HIF-1 alpha promoter that regulates basal HIF-1 alpha expression.