Activating transcription factor 2 (ATF2) down-regulates hepatitis B virus X promoter activity by the competition for the activating protein I binding site and the formation of the ATF2-Jun heterodimer

The hepatitis B viral X promoter is known to be positively autoregulated by its own HBx protein, which also interacts with many cellular regulatory proteins, We investigated the effect of activating transcription factor 2, (ATF2) on the activity of the PL promoter. Cotransfection of the ATF2 expression vector with a X promoter-chloramphenicol acetyltransferase plasmid repressed the X promoter activity in HepG2 cells, HBx activated activating protein 1 (AP-1)-mediated transcription through the hepatitis B virus E element by 35-fold, while its activation activity was inhibited in the presence of ATF2, suggesting that ATF2 inhibited the autoactivation of X promoter by HBx and basal transcription mediated by AP-1. Since the binding sites of AP-1 and ATF2 in the hepatitis B virus E element overlap, the repression of X promoter activity by ATF2 is everted by the competition for the AP-1 binding site and the formation of the ATF2-Jun heterodimer as in the casa of the consensus AP-1 element. However, the small X promoter had a ATF2 binding site and was activated by ATF2. These results suggest that the syntheses of X proteins are differentially regulated by ATF2.