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  • Title: Evidence for the presence of a guanine quadruplex forming region within a polypurine tract of the hypoxia inducible factor 1alpha promoter.
    Author: De Armond R, Wood S, Sun D, Hurley LH, Ebbinghaus SW.
    Journal: Biochemistry; 2005 Dec 13; 44(49):16341-50. PubMed ID: 16331995.
    Abstract:
    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.
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