Structure of the biologically relevant G-quadruplex in the c-MYC promoter.
The nuclease hypersensitivity element III1 (NHE III1) in the c-MYC promoter controls up to 80-90% of the transcriptional activity of this gene. We have demonstrated that the guanine-rich strand of the NHE III1 forms a G-quadruplex consisting of a mixture of four biologically relevant loop isomers that function as a silencer element. NMR studies have shown that these G-quadruplexes are propeller-type parallel structures consisting of three stacked G-tetrads and three double-chain reversal loops. An NMR-derived solution structure for this quadruplex provides insight into the unusual stability of the structure. This structure is a target for small molecule inhibitors of c-MYC gene expression.
Yang
Danzhou
D
University of Arizona, College of Pharmacy, Tucson, AZ 85721, USA.
Hurley
Laurence H
LH
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D054856:G-Quadruplexes; D006151:Guanosine / Q000737:chemistry*; D006801:Humans; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics*; D037941:Silencer Elements, Transcriptional; D014158:Transcription, Genetic
D016271:Proto-Oncogene Proteins c-myc; D006151:Guanosine; D004247:DNA