| Functional cooperation among transcription factors is a fundamental strategy by which transcription factors regulate promoter activity. Binding sites for both Sp1 and E2F frequently occur in TATA-less promoters in close proximity to one another. Previous studies indicated that Sp1 and E2F1 functionally cooperate with other factors to activate transcription and confer growth regulation (Seto, E., Lewis, B., and Shenk, T., Nature 365: 462–464, 1993; Lin, S-Y., Black, A. R., Kostic, D., Pajovic S., Hoover, C. N., and Azizkhan, J. C., Mol. Cell. Bio. 16:1668–1675, 1996; van Ginkel et al. van Ginkel, P. R., Hsiao, K. M., Schjerven, H., and Farnham, P. J., J. Bio. Chem. 272:18367–18374, 1997; Krainc, D., Bai, G., Okamoto, S., Carles, M., Kusiak, J. W., Brent, R. N., and Lipton, S. A., J. Bio. Chem. 273: 26218–26224, 1998). In addition, Sp1 and E2F1 have been shown to physically interact with each other both in vivo and in vitro and the interaction was thought to be critical for their functional cooperation (Lin, S-Y., Black, A. R., Kostic, D., Pajovic S., Hoover, C. N., and Azizkhan, J. C., Mol. Cell. Bio. 16:1668–1675, 1996).; In this study, Sp1 and E2F1 have been found to functionally cooperate with each other in several TATA-less promoters, including dihydrofolate reductase, human DNA polymerase a, mouse thymidylate synthase, and mouse thymidine kinase. Data from this study show that a single Sp1 site is sufficient to stimulate transcription from several TATA-less promoters and E2F1 alone can stimulate transcription as long as no repressive element is present in the same promoter. Despite the direct physical interaction between Sp1 and E2F1, it is not essential for their functional cooperation.; In the DNA polymerase a promoter, several regulatory elements in addition to the Sp1 and E2F sites can modulate the activation by Sp1 and/or E2F1. Moreover, data demonstrated that several previously unidentified elements, including a second E2F site, contribute to the relatively high activation of the DNA polymerase α promoter by E2F1 alone. Furthermore, different Sp1 and E217 binding sequences differ in their abilities to mediate responses to exogenous Sp1 and E2F1. Overall, the degree of functional cooperation between Sp1 and E2F1 is determined by the combined effect of physical interaction and promoter-specific features. |
