Here, we report that an E-box element located within the human topoisomerase IIIα (hTOP3α) gene promoter acts as a cell type-specific enhancer. The upstream stimulatory factor (USF) was shown to specifically recognize the mutationally sensitive E-box element. When assayed by transient transfection with hTOP3α promoter-dependent reporter genes, USF is transcriptionally active in HeLa cells but lacks transcriptional activity in Saos-2 cells. The hTOP3α mRNA level in Saos-2 cells was reduced to about 30% of the level observed for HeLa cells, suggesting that the inactivity of USF in hTOP3α promoter activity may be the cause of the marked reduction of hTOP3α mRNA levels in Saos-2 cells. Using transient transfection assays in HeLa cells, we demonstrated that ectopically expressed USF2, but not USF1, was capable of activating hTOP3α transcription through the E-box element. However, USF2 did not stimulate hTOP3α promoter activity in Saos-2 cells. This cell type-specific regulation of promoter activity by USF2 may provide a mechanism for the differential expression of hTOP3α in various tissues and during developmental stages.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Cell Biology