Transcriptional activation by artificial recruitment in mammalian cells.

We show that the typical "nonclassical" activator, which comprises a fusion protein bearing a component of the transcriptional machinery fused to a DNA-binding domain, activates transcription in mammalian cells only weakly when tested with an array of promoters. However, as found in analogous "artificial recruitment" experiments performed in yeast, these activators work synergistically with "classical" activators. The effect of the classical activator in such experiments requires that it be tethered to DNA, a requirement that cannot be overcome by expression of that classical activator at high levels. The effect of the one nonclassical activator that does elicit significant levels of transcription when working alone (i.e., that bearing TATA box-binding protein) is strongly influenced by promoter architecture. The results, consistent with those of analogous experiments in yeast [see the accompanying paper: Gaudreau, L., Keaveney, M., Nevado, J., Zaman, Z., Bryant, G. O., Struhl, K. & Ptashne, M. (1999) Proc. Natl. Acad. Sci. USA 96, 2668-2673], suggest that classical activators, presumably by virtue of their abilities to interact with multiple targets, have a functional flexibility that nonclassical activators lack.