Regulation of mouse DNA topoisomerase IIIalpha gene expression by YY1 and USF transcription factors.

To investigate the mechanisms responsible for the regulation of DNA topoisomerase IIIalpha (TOP3alpha) gene expression, the promoter region of the mouse gene has been cloned and analyzed. The promoter region is moderately high in GC content and lacks a canonical TATA box, typical for promoters of a number of housekeeping genes. Transient expression of a luciferase reporter gene under the control of serially deleted 5'-flanking sequences demonstrated that the 34-bp region from -137 to -170 upstream of the transcription initiation site contains a positive regulatory element(s) for the efficient expression of mouse TOP3alpha gene. Combined analyses by gel mobility shift and supershift assays revealed that both YY1 and USF transcription factors were capable of binding to the 34-bp region. When YY1 and USF-binding elements were selectively mutated, the luciferase activity of the resulted constructs was greatly reduced, indicating that both YY1 and USF function as transcriptional activators. Interestingly, YY1 and USF-binding elements are conserved in both human and mouse TOP3alpha promoters. This suggests that mammalian TOP3alpha genes may possess a common mechanism of transcription regulation through these elements.