Identification of a G-quadruplex forming sequence in the promoter of UCP1.

G-quadruplexes are higher-order nucleic acid structures formed in G-rich sequences in DNA or RNA. G-quadruplexes are distributed in many locations in the human genome, including promoter regions, and are viewed as promising therapeutic targets. Uncoupling protein-1 (UCP1) is a mitochondrial thermogenic gene critical for energy expenditure in the form of heat in the brown adipose tissue. UCP1 is only expressed during brown fat cell differentiation and is a candidate target for treating obesity. However, the regulation of UCP1 expression is not clear. We reported here that a G-quadruplex forming sequence exists in the promoter of UCP1. The 5,10,15,20-tetra(Nmethyl- 4-pyridyl) porphyrin (TMPyP4) enhanced cellular expression of UCP1 and destabilized the G-quadruplex formed by the sequence from the promoter of UCP1. Mutations in the G-quadruplex regulated the cellular activity of UCP1 promoter as evidenced by a UCP1-promoter luciferase assay. These results suggest that G-quadruplex structure is a potential target to regulate the expression of UCP1.