The dimer formed by the ATF-2 and c-Jun transcription factors is one of the main 
components of the human interferon-beta enhanceosome. Although these two 
transcription factors are able to form two homodimers and one heterodimer, it is 
mainly the heterodimer that participates in the formation of this enhanceosome, 
binding specifically to the positive regulatory domain IV (PRDIV) site of the 
enhancer DNA. To understand this surprising advantage of the heterodimer, we 
investigated the association of these transcription factors using fragments 
containing the basic DNA-recognition segment and the basic leucine zipper domain 
(bZIP). It was found that the probability of forming the hetero-bZIP 
significantly exceeds the probability of forming homo-bZIPs, and that the 
hetero-bZIP interacts more strongly with the PRDIV site of the interferon-beta 
enhancer, especially in the orientation that places the folded ATF-2 basic 
segment in the upstream half of this asymmetric site. The effect of salt on the 
formation of the ATF-2/c-Jun dimer and on its ability to bind the target PRDIV 
site showed that electrostatic interactions between the charged groups of these 
proteins and with DNA play an essential role in the formation of the asymmetric 
ATF-2/c-Jun/PRDIV complex.