Sigmoid curve and non-additive activation by multiple regulatory sites are two typical manifestations of transcriptional synergy in eukaryotes. There are three possible mechanisms for synergistic regulation: interaction between activators, cooperative binding of activators to DNA upstream sites and cooperative interaction of site-bound activators with GTM (general transcriptional machinery) components. All these mechanisms involve direct or indirect interactions among multiple activators that bind to upstream regulatory sites. The pre-bound activators can facilitate the binding of free ones through these interactions and this underlines the basis of synergistic activation.