Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c- MYC transcription

• DOI: 10.1073/pnas.182256799
• Publication Date: 2002-09-03T19:58:55Z
• Authors: Adam Siddiqui-Jain; Cory L. Grand; David J. Bearss; Laurence H. Hurley
• Keywords: G-quadruplex; Transcription; Nuclease; Response element

The nuclease hypersensitivity element III 1 upstream of the P1 promoter c- MYC controls 85–90% transcriptional activation this gene. We have demonstrated that purine-rich strand DNA in region can form two different intramolecular G-quadruplex structures, only one which seems to be biologically relevant. This relevant structure is kinetically favored chair-form G-quadruplex, destabilized when mutated with a single G → A transition, resulting 3-fold increase basal activity promoter. cationic porphyrin TMPyP4, has been shown stabilize structure, able suppress further activation. These results provide compelling evidence specific formed functions as repressor element. Furthermore, we establish principle transcription controlled by ligand-mediated stabilization.