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 journalArticle

116 Citations (Scopus)

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

Fingerprint

G-Quadruplexes
Plasmids
Guanine
Drug Delivery Systems
Thermodynamics
Oligonucleotides
Nucleotides
Observation

ASJC Scopus subject areas

  • Genetics

Cite this

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

In: Nucleic Acids Research, Vol. 39, No. 20, 11.2011, p. 9023-9033.

Research output: Contribution to journalArticle

@article{90ce1859337e494fa5927b707a6f0b7a,
title = "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",
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.",
author = "Mathad, {Raveendra I.} and Emmanuel Hatzakis and Jixun Dai and Danzhou Yang",
year = "2011",
month = "11",
doi = "10.1093/nar/gkr612",
language = "English (US)",
volume = "39",
pages = "9023--9033",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "20",

}

TY - JOUR

T1 - C-MYC promoter G-quadruplex formed at the 5′-end of NHE III 1 element

T2 - Insights into biological relevance and parallel-stranded G-quadruplex stability

AU - Mathad, Raveendra I.

AU - Hatzakis, Emmanuel

AU - Dai, Jixun

AU - Yang, Danzhou

PY - 2011/11

Y1 - 2011/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80455168261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80455168261&partnerID=8YFLogxK

U2 - 10.1093/nar/gkr612

DO - 10.1093/nar/gkr612

M3 - Article

C2 - 21795379

AN - SCOPUS:80455168261

VL - 39

SP - 9023

EP - 9033

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 20

ER -