Hepadnavirus enhancer and its binding proteins.

In the hepadnavirus enhancer region, a 33 bp DNA sequence is strongly conserved among mammalian hepadnavirus genomes. To elucidate the role of the sequence, we tested enhancer activities and capability to form DNA-protein complex of several synthetic DNAs. Not only two tandem copies of a 46 bp DNA covering the sequence but also two tandem copies of a 23 bp in the sequence exhibit enhancer activity. Also the activity was augmented by treatment of a tumor promoter, TPA. DNA binding proteins complexes with the 23 bp DNA were augmented in extracts of HepG2 or HeLa cells stimulated with TPA. These results imply that the conserved sequence of hepadnavirus enhancer is a TPA-inducible enhancer which is transactivated by ubiquitous DNA-binding proteins. We presented results showing that DNA-protein complexes with a 23 bp DNA are similar to but distinct from those with a TPA-responsive element DNA, the recognition site for c-jun/fos products. We also presented results suggesting that hepadnavirus X protein may not directly or indirectly affect DNA-protein complex formation with the conserved sequence in the hepadnavirus enhancer.