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 lambda repressor interact to promote binding of these proteins to DNA, a reaction that is crucial at the repressor concentrations found in lysogens. In this case one of the bound dimers activates transcription, evidently by touching RNA polymerase. 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 site. In this paper we show that synergistic activation by each of several GAL4 derivatives involves a mechanism different from that illustrated by the lambda 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 activator. 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.
Carey
M
M
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Lin
Y S
YS
Green
M R
MR
Ptashne
M
M
D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins; D003850:Deoxyribonuclease I / Q000378:metabolism; D004357:Drug Synergism; D004926:Escherichia coli; D005656:Fungal Proteins / Q000378:metabolism / Q000494:pharmacology*; D006367:HeLa Cells / Q000378:metabolism; D010750:Phosphoproteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins; D018139:Simplexvirus; D015534:Trans-Activators / Q000494:pharmacology; D014157:Transcription Factors / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C064255:GAL4 (1-147) protein, S cerevisiae; C052130:GAL4 protein, S cerevisiae; D010750:Phosphoproteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA; D003850:Deoxyribonuclease I