A Combinatorial Mechanism for Determining the Specificity of E2F Activation and Repression

Various studies have detailed the role of E2F proteins in both transcription activation and repression. Further work has shown that distinct promoter elements, but comprising the same E2F recognition motif, confer positive or negative E2F control and that this reflects binding of either activator or repressor E2F proteins respectively. We now show that the specificity of binding of an activator or repressor E2F protein is determined by adjacent sequences that bind a cooperating transcription factor. We propose that the functional E2F element is a module comprising not only the E2F binding site but also the adjacent site for the cooperating transcription factor.