TFII-I Enhances Activation of the c- fos Promoter through Interactions with Upstream Elements

Abstract

ABSTRACT The transcription factor TFII-I was initially isolated as a factor that can bind to initiator elements in core promoters. Recent evidence suggests that TFII-I may also have a role in signal transduction. We have found that overexpression of TFII-I can enhance the response of the wild-type c- fos promoter to a variety of stimuli. This effect depends on the c- fos c- sis –platelet-derived growth factor-inducible factor binding element (SIE) and serum response element (SRE). There is no effect of cotransfected TFII-I on the TATA box containing the c- fos basal promoter. Three TFII-I binding sites can be found in c- fos promoter. Two of these overlap the c- fos SIE and SRE, and another is located just upstream of the TATA box. Mutations that distinguish between serum response factor (SRF), STAT, and TFII-I binding to the c- fos SIE and SRE suggest that the binding of TFII-I to these elements is important for c- fos induction in conjunction with the SRF and STAT transcription factors. Moreover, TFII-I can form in vivo protein-protein complexes with the c- fos upstream activators SRF, STAT1, and STAT3. These results suggest that TFII-I may mediate the functional interdependence of the c- fos SIE and SRE elements. In addition, the ras pathway is required for TFII-I to exert its effects on the c- fos promoter, and growth factor stimulation enhances tyrosine phosphorylation of TFII-I. These results indicate that TFII-I is involved in signal transduction as well as transcriptional activation of the c- fos promoter.