A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives

IN prokaryotes and eukaryotes many gene activators work synergistically. For example, two dimers of λ represser interact to promote binding of these proteins to DNA, a reaction that is crucial at the repressor concentrations found in lysogens1. In this case one of the bound dimers activates transcription, evidently by touching RNA polymerase2. In another example, the yeast transcriptional activator GAL4, which can stimulate transcription in many eukaryotes, binds to multiple sites on DNA to activate transcription synergistically; the presence of two such sites can elicit a level of transcription more than twice that found with a single site3. In this paper we show that synergistic activation by each of several GAL4 derivatives involves a mechanism different from that illustrated by the λ repressor: multiple activator molecules can work synergistically under conditions in which their binding sites on DNA are saturated. The accompanying paper shows that under similar conditions of activator excess, GAL4 derivatives work synergistically with a heterologous mammalian gene activator4. These results support the idea that eukaryotic activators can cooperate not by directly interacting but by simultaneously touching some component(s) of the transcriptional machinery.