It is well accepted that the sequence of transcription Sorafenib 284461-73-0 factor binding sites can often differ in different parts of the genome. Two constructs were generated by site directed mutagenesis. The first construct had one base pair added to match the consensus human Oct-1 binding site and the second had a two base pair alteration at the start of the sequence. Upon Oct-1 transcription factor overexpression, significant increases in luciferase expression were seen to be greatest with the construct Paclitaxel containing the one base pair addition as well as controls that contained the 17 bp region. This increase was however not seen with the construct containing the two base pairs modification. In line with a previous study, substitution of the first two base pairs resulted in the loss of Oct- 1 transcription factor inducibility. Altogether, this result strongly suggested that the 17 bp region delineated from conserved region 1 contains an Oct-1 binding site and that the substitution of the first two bases within the consensus sequence disrupted this binding. This indicates that the crucial nucleotides for the transcription factor binding are located at the start of the Oct-1 sequence. Furthermore, it was also shown that the presence of an additional base within the pGL3-Basic::MUT1 construct to match the consensus Oct-1 binding site indeed increased the luciferase reporter expression. The presence of this extra sequence may strengthen Oct-1 transcription factor binding in the presence of abundant transcription factor. The findings of the current study are important and may influence future clinical therapeutic strategies for FRDA. It is hypothesized that any increase in frataxin levels should prove beneficial, while a several-fold increase could be sufficient to halt disease progression. Induction of FXN gene expression directly addresses the primary issue of frataxin deficiency. Therapies for hemoglobinopathies have been developed based on knowledge of gene regulation. In b-thalassemia, where there is a disruption of bglobin production, increasing c-globin gene expression ameliorates disease severity. As Oct-1 reduces the transcription of cglobin, a decrease in Oct-1 binding results in an increase in cglobin gene expression. In one study, decoy oligonucleotides containing the Oct-1 consensus sequence were able to compete with the endogenous c-globin cis-regulatory elements in vitro leading to the removal of the transcription factor from the endogenous targets and thus altering transcription of the target gene. Although this is an example of the removal a transcription factor in order to acquire a higher level of gene expression, it does give an insight into the possibility in modulating the level of the Oct-1 transcription factor to influence FXN gene expression as a potential clinical therapy for FRDA. In conclusion, we have demonstrated that highly conserved regions upstream of the FXN gene influence gene expression.