Transcriptional activation of the interferon-beta (IFN-beta) gene requires 
assembly of an enhanceosome containing the transcription factors ATF-2/c-Jun, 
IRF-3/IRF-7, NF-kappaB and HMGI(Y). These factors cooperatively bind a composite 
DNA site and activate expression of the IFN-beta gene. The 3.0 A crystal 
structure of the DNA-binding domains of ATF-2/c-Jun and two IRF-3 molecules in a 
complex with 31 base pairs (bp) of the PRDIV-PRDIII region of the IFN-beta 
enhancer shows that association of the four proteins with DNA creates a 
continuous surface for the recognition of 24 bp. The structure, together with in 
vitro binding studies and protein mutagenesis, shows that protein-protein 
interactions are not critical for cooperative binding. Instead, cooperativity 
arises mainly through nucleotide sequence-dependent structural changes in the 
DNA that allow formation of complementary DNA conformations. Because the binding 
sites overlap on the enhancer, the unit of recognition is the entire nucleotide 
sequence, not the individual subsites.