EVIDENCE FOR 2 MODES OF COOPERATIVE DNA-BINDING IN-VIVO THAT DO NOT INVOLVE DIRECT PROTEIN-PROTEIN INTERACTIONS

Background: The promoter regions of most eukaryotic genes contain bind ing sites for more than one transcriptional activator and these activa tors often bind cooperatively to promoters. The most common type of co operativity is supported by direct protein-protein interactions. Recen t studies have shown that proteins that do not specifically interact w ith one another can bind cooperatively to chromatin in vitro, probably by the localized destabilization of nucleosome structure by one facto r, facilitating binding of another to a nearby site. This mechanism do es not require that the transcription factors have activation domains. We have examined whether this phenomenon occurs in vivo. Results: Unr elated non-interacting proteins can bind DNA cooperatively in yeast ce lls; this cooperative binding can contribute significantly to transcri ptional activation, does not require that both factors have activation domains and is only operative over relatively short distances. In add ition to this 'short-range' mechanism, unrelated non-interacting prote ins can bind cooperatively to sites separated by hundreds of base pair s, so long as both have potent activation domains. Conclusion: Coopera tive binding of transcription factors in vivo can occur by several mec hanisms, some of which do not require direct protein-protein interacti ons and which cannot be detected in vitro using naked DNA templates. T hese findings must be taken into account when evaluating mechanisms fo r synergistic transcriptional activation. (C) Current Biology Ltd ISSN 0960-9822.