Structure of the biologically relevant G-quadruplex in the c-MYC promoter

Nucleosides Nucleotides Nucleic Acids. 2006;25(8):951-68. doi: 10.1080/15257770600809913.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics
  • G-Quadruplexes
  • Guanosine / chemistry*
  • Humans
  • Nucleic Acid Conformation
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-myc / genetics*
  • Silencer Elements, Transcriptional*
  • Transcription, Genetic*

Substances

  • Proto-Oncogene Proteins c-myc
  • Guanosine
  • DNA