The flanking sequence contributes to the immobilisation of spermine at the G-quadruplex in the NHE (nuclease hypersensitivity element) III1 of the c-Myc promoter

Abstract

Defining the molecular basis of the DNA sequence selectivity of polyamine binding is central to understanding polyamine-dependent gene expression. We have studied, by selective NMR experiments, the variation of spermine mobility and conformation in the presence of G-quadruplexes formed by sequences of the purine-rich strand of the c-Myc promoter, nuclease hypersensitivity element III1 (NHE III1). All the NHE quadruplexes restrict spermine mobility and induce a spermine conformational change but the most effective immobilisation occurs when all five G-tracts of the NHE III1 are present. This suggests structure within the nucleotides flanking the G-quadruplex has a role in immobilising spermine.

Keywords: DNA recognition; NMR spectroscopy; Quadruplex DNA; Spermine; c-Myc regulation.