Na+ specific structural transition in d(CGGGGG)6C: a promoter segment of human Arachidonate 5-lipoxygenase (ALOX5) gene

For decades, G-quadruplexes (GQs) structures have been overwhelmingly studied and considered the most topologically diverse molecules. These non-Watson-Crick structures form at guanine-rich sequences, shaping into stacked G•G•G•G tetrads and stabilised by Hoogsteen/reverse Hoogsteen hydrogen bonding. Their folding pattern and stability depend on ionic conditions, strand polarity, and loop composition. The biological validation of these structures is being explored with great interest. Using bioinformatics, we showed that a 37-mer GC–rich DNA segment (Lipo37), flanked and associated with various transcription factors (TFs), is fully conserved at the promoter of the Human Arachidonate 5-lipoxygenase (ALOX5) gene. Further, employing biophysical studies using gel electrophoresis, circular dichroism (CD), and UV-thermal denaturation profiles, we comprehensively demonstrated that in the presence of Li + and K + , Lipo37 sequence [d(CGGGGG) 6 C] forms a highly stable intramolecular GQ exhibiting parallel topology, whereas distinctively, the antiparallel topology, observed at low Na + concentration switches to a completely parallel topology, with increasing Na + concentration. However, K + did not exhibit any such concentration-dependent transition and persistently endured the parallel topology. Hitherto, such a Na + -mediated topological transition, relative to sodium (Na+) ion concentration, by a non-telomeric genomic sequence Lipo37 [d(CGGGGG) 6 C], has not been proposed. Our results enrich the reports on known structural transitions of GQs. The knowledge of peculiar GQ geometries and transitions may have implications for their specific recognition by transcription factors (TFs)/proteins and ligands. • A promoter sequence of the Human ALOX5 gene exhibits Na + specific structural transition. • G-quadruplexes formed here, display a significant structural polymorphism, adopting various topologies. • Bioinformatics showed that Lipo37 is flanked and associated with various transcription factors (TFs).