Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences
David A. Johnson
Marc W. Harrold
DNA bending, TFO, transcription regulation
The conformation of DNA has been shown to play an important role in the regulation of gene expression. A consequence of this finding is that agents that alter the conformation of DNA should also affect the regulation of gene expression. To explore this, we used tethered-triple helix oligonucleotides (TFO) to bend DNA. We show that the expression of a luciferase gene is regulated by the presence of an induced DNA bend. Bends occurring in the same orientation as RNA polymerase binding result in a 93% increase in expression. In contrast, bends induced in that opposite direction resulted in a 51% decrease in expression. These results prompted us to investigate the synthesis of three small molecules with the potential to induce a sequence selective bend in DNA. These studies revealed that the compounds were able to induce a DNA bend counter to an intrinsic bend present in a target DNA fragment.
Bednarski, D. (2007). Gene Regulation Through Artificially Induced DNA Conformational Changes (Master's thesis, Duquesne University). Retrieved from http://ddc.duq.edu/etd/29