Self-organization of G-quadruplex structures in the hTERT core promoter stabilized by polyaminic side chain perylene derivatives

hTERT core promoter regulates telomerase transcription in human cells, thus its structural features are of large interest. We have found that the G-rich hTERT core promoter region, corresponding to the major DNase I hypersensitive site in chromatin organization, contains nine putative G-quadruplex forming sequences (PQS) and is unfavorable for nucleosome formation. Here we show that four PQS are effectively able to form stable parallel intramolecular G-quadruplexes, using PAGE and CD spectroscopy analysis. The PQS-region, as a whole, appears to be organized in three self-interacting G-quadruplexes, probably giving rise to a helicoidal superstructure, as shown by CD and polymerase stop assay.POL-HPDI drugs, that we previously found useful in selectively stabilizing telomeric G-quadruplex, are able to stabilize both the single intramolecular G-quadruplex and the PQS-region superstructure. The features of their induced CD spectra suggest that POL-HPDIs bind to single G-quadruplexes and to whole PQS-region superstructure, mainly by end-stacking interactions.

Graphical AbstractResearch Highlights► The hTERT core promoter contains nine putative G-quadruplex forming sequences (PQS). ► Four PQS are effectively able to form parallel intramolecular G-quadruplexes. ► The PQS-region appears to be organized in three self-interacting G-quadruplexes. ► POL-HPDIs stabilize both the single G-quadruplexes and the PQS-region superstructure.