C-MYC promoter G-quadruplex formed at the 5′-end of NHE III 1 element: Insights into biological relevance and parallel-stranded G-quadruplex stability

Raveendra I. Mathad, Emmanuel Hatzakis, Jixun Dai, Danzhou Yang

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

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 III1, 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 III1 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 III1 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.

Original languageEnglish (US)
Pages (from-to)9023-9033
Number of pages11
JournalNucleic acids research
Volume39
Issue number20
DOIs
StatePublished - Nov 2011

ASJC Scopus subject areas

  • Genetics

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