Structure of the Biologically Relevant G-Quadruplex in The c-MYC Promoter

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.

Keywords:

• c-MYC
• G-quadruplex
• Transcriptional control

Presented at the XVI International Roundtable, September 12–16, 2004, Minneapolis, Minnesota