G-quadruplex superstructure in the hTERT core promoter: stabilization by monomer self-stacking

G-quadruplex-forming are widespread in eukaryotic genomes. In particular, G-quadruplex motifs have been found in the promoter region of 40% human genes. One of these genes is hTERT, encoding the catalytic subunit of human telomerase, whose up-regulated expression is responsible for the unlimited proliferative potential of most cancer cells. hTERT core promoter exhibits a high potential for G-quadruplex formation, containing nine partially overlapping PQS (putative quadruplex sequence) in a G-rich region of 68 nucleotides. Here we show the formation of a superstructure in the hTERT promoter deriving from the simultaneous folding of three adjacent G-quadruplex structures. Interestingly, G-quadruplex ligands are able to stabilize hTERT G-quadruplex structures and to alter transcription from the hTERT promoter, suggesting that the formation of a G-quadruplex superstructure could play a role in regulating gene transcription.