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Evidence for the Presence of a Guanine Quadruplex Forming Region within a Polypurine Tract of the Hypoxia Inducible Factor 1α Promoter†
journal contribution
posted on 2005-12-13, 00:00 authored by Richard De Armond, Stacey Wood, Daekyu Sun, Laurence H. Hurley, Scot W. EbbinghausThe promoter of the hypoxia inducible factor 1 alpha (HIF-1α) 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-1α expression. Oligonucleotides
representing this region of the HIF-1α 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-1α promoter that regulates basal HIF-1α
expression.
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Guanine Quadruplex Forming Regiontranscription factor binding sitescationic porphyrin TmPyP 4unimolecular quadruplexHIFDNA polymerase arrest assaysbasalquadruplex structurePolypurine Tractproduct telomestatinquadruplex binding compoundsregionhypoxia inducible factor 1promoterquadruplex formationelectrophoretic mobility shiftexpression
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