Proximal promoter-independent activation of the far-upstream FGF-inducibleresponse element of syndecan-1 gene

Far upstream enhancers are predicted to act by looping and activating gener al transcription factors on core promoters and to require proximal promoter sequences for appropriate gene activation in time and space. We have previ ously described an FGF-inducible response element (FiRE) located far upstre am on the syndecan-1 gene. The FiRE is activated specifically by members of the fibroblast growth factor (FGF) family in NIH3T3 cells. Here we describ e the requirements of syndecan-1 proximal promoter for the activation of Fi RE by FGF-2. Transient and stable transfections revealed that neither proxi mal promoter SP1 sites nor TATA-box are required for the FGF-8 induced acti vation of FiRE. Notably, the enhancer is activated in both orientations by FGF-8 even in the absence of proximal promoter. Importantly, removal of the promoter did not affect the growth factor specificity of FiRE. Proximal pr omoter independent activation of syndecan-1 gene by FGF-8 might be required during development when syndecan-1 proximal promoter needs to be largely a ttenuated but simultaneous transient and rapid FGF-S induced transcription is required. (C) 2000 Academic Press.