Evidence for the presence of a guanine quadruplex forming region within a polypurine tract of the hypoxia inducible factor 1α promoter

Richard De Armond, Stacey Wood, Daekyu Sun, Laurence H. Hurley, Scot W. Ebbinghaus

Research output: Contribution to journalArticle

203 Scopus citations

Abstract

The 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-Iα 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.

Original languageEnglish (US)
Pages (from-to)16341-16350
Number of pages10
JournalBiochemistry
Volume44
Issue number49
DOIs
StatePublished - Dec 13 2005

ASJC Scopus subject areas

  • Biochemistry

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