title: c-MYC promoter G-quadruplex formed at the 5'-end of NHE III1 element: insights into biological relevance and parallel-stranded G-quadruplex stability.
abstract: We studied the structures and stabilities of G-quadruplexes formed in Myc1234, the region containing the four consecutive 5' runs of guanines of c-MYC promoter NHE III(1,) which have recently been shown to form in a supercoiled plasmid system in aqueous solution. We determined the NMR solution structure of the 1:2:1 parallel-stranded loop isomer, one of the two major loop isomers formed in Myc1234 in K(+) solution. This major loop isomer, although sharing the same folding structure, appears to be markedly less stable than the major loop isomer formed in the single-stranded c-MYC NHE III(1) oligonucleotide, the Myc2345 G-quadruplex. Our NMR structures indicated that the different thermostabilities of the two 1:2:1 parallel c-MYC G-quadruplexes are likely caused by the different base conformations of the single nucleotide loops. The observation of the formation of the Myc1234 G-quadruplex in the supercoiled plasmid thus points to the potential role of supercoiling in the G-quadruplex formation in promoter sequences. We also performed a systematic thermodynamic analysis of modified c-MYC NHE III(1) sequences, which provided quantitative measure of the contributions of various loop sequences to the thermostabilities of parallel-stranded G-quadruplexes. This information is important for understanding the equilibrium of promoter G-quadruplex loop isomers and for their drug targeting.
authors.affiliation: College of Pharmacy, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Raveendra I
authors.initials: RI
authors.lastname: Mathad
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hatzakis
authors.forename: Jixun
authors.initials: J
authors.lastname: Dai
authors.forename: Danzhou
authors.initials: D
authors.lastname: Yang
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D054856:G-Quadruplexes; D016259:Genes, myc; D007536:Isomerism; D008958:Models, Molecular; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009691:Nucleic Acid Denaturation; D011188:Potassium / Q000737:chemistry; D011401:Promoter Regions, Genetic
chemical_list: D004247:DNA; D011188:Potassium