| Tyrosine hydroxylase is a gene found on the short arm of chromosome 11 within an important cluster of genes coding for the Insulin Linked Polymorphic Region, Insulin, and IGF2 (Gene ID:7054). Tyrosine hydroxylase protein is responsible for the conversion of L-Tyrosine to L-DOPA, which is the first and rate-limiting step in the biosynthesis of catecholamines such as dopamine, epinephrine, and norepinephrine. Here we have investigated the prevalence of guanine rich sequences within the promoter that could putatively form a non-B-DNA structure known as a G quadruplex. A G quadruplex is formed by the stacking of two or more g tetrads. G tetrads form when 4 guanine residues come together through Hoogsteen hydrogen bonding, forming a planar structure, which, in turn can stack on top of each other to form the quadruplex. Previous studies have shown that the presence of a quadruplex within the promoter region of a gene can have an effect on the regulation of the gene, either positive or negative. In addition to confirming multiple quadruplex formations within the tyrosine hydroxylase promoter, we have investigated the kinetic and thermodynamic properties of this ensemble of quadruplexes in vitro. Our findings have laid the groundwork for the discovery of the functional role of this structure in vivo. Additionally, the deconvolution of this quadruplex in vitro will indicate possible polymorphisms that could happen in vivo. These studies provide information that will help the scientific community in understanding the complicated regulation of the tyrosine hydroxylase gene, and could provide insight into the underlying mechanism of diseases in which tyrosine hydroxylase expression levels are key, including Parkinson's disease, bipolar disorder, and schizophrenia. |
