Synergistic activation of transcription by physiologically unrelated transcription factors through cooperative DNA-Binding

Most eukaryotic promoters contain binding sites for several different transcription factors, which often act synergistically. Mechanistically, synergy is ascribed either to cooperative DNA-binding of the factors to the promoter or to some type of 'multiple contact' mechanism in which each activator performs a different task in stimulating the transcription machinery. Here, it is shown that the yeast activators Gal4 and Put3 bind to DNA cooperatively in vivo and can activate transcription synergistically from certain synthetic promoters. Normally, Gal4 and Put3 bind to completely different promoters and activate physiologically unrelated sets of genes and it is extremely unlikely that they have evolved direct protein-protein contacts. These studies add to a growing body of evidence that binding of proteins to nearby sites in chromatin is intrinsically cooperative and suggest that many examples of synergy ascribed to multiple contact mechanisms may instead involve non-traditional cooperative DNA-binding.