De Armond Richard, Wood Stacey, Sun Daekyu, Hurley Laurence H, Ebbinghaus Scot W
Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, Arizona 85724-5024, USA.
Biochemistry. 2005 Dec 13;44(49):16341-50. doi: 10.1021/bi051618u.
The promoter of the hypoxia inducible factor 1 alpha (HIF-1alpha) gene has a polypurine/polypyrimidine tract (-65 to -85) overlapping or adjacent to several putative transcription factor binding sites, and we found that mutagenesis of this region diminished basal HIF-1alpha expression. Oligonucleotides representing this region of the HIF-1alpha 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-1alpha promoter that regulates basal HIF-1alpha expression.
缺氧诱导因子1α（HIF-1α）基因的启动子有一个多嘌呤/多嘧啶序列（-65至-85），与几个假定的转录因子结合位点重叠或相邻，并且我们发现该区域的诱变会降低基础HIF-1α的表达。通过电泳迁移率变动分析、化学探针分析、圆二色性分析和DNA聚合酶终止分析对代表HIF-1α启动子该区域的寡核苷酸进行了分析。发现在钾存在的情况下，富含鸟嘌呤的链会形成一个平行的单分子四链体，两种已知的四链体结合化合物，即阳离子卟啉TmPyP4和天然产物端粒抑素会进一步使其稳定，而TmPyP4的位置异构体TmPyP2则不能稳定四链体的形成。这些数据表明，在调节基础HIF-1α表达的HIF-1α启动子区域可能会形成四链体结构。
