DNA Triplex Formation on the Granulocyte-Macrophage Colony-Stimulating Factor Gene Proximal Promoter

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hemapoietic cytokine that has been implicated in certain pathological conditions. We have previously demonstrated that an intermolecular DNA triplex formation on a target overlapping the NF-kB binding site on the GM-SCF proximal promoter inhibited gene transcription. A substitution of guanine (G) for thymine (T) in the triplex forming oligonucleotide (TFO) opposite a C:G inversion in the underlying duplex led to a significant increase in the TFO binding affinity and its ability to block NF-kB protein binding to the DNA. However, the substitution did not significantly affect the inhibition of GM-CSF promoter reporter gene activity by the TFO in Jurkat T cells.