Binding of tissue-specific factors to the enhancer sequence of hepatitis B virus.

We have identified tissue-specific factors, in human hepatoma cells, that bind specifically to the transcriptional enhancer sequence of the human hepatitis B virus (HBV). Two different types of protein factor were found in nuclear extracts of hepatoma cells by gel mobility shift assay. One factor was observed in human hepatoma cells but not in human kidney, lung, or vein cells, or in embryonic mouse cells. The other was discovered in both human hepatoma cells and human vein cells. DNase I footprint analysis, using the enhancer fragment (164 bp, AccI-SphI) from HBV, revealed that two specific sites are recognized by the nuclear factors. These sites contain consensus octamer sequences which have been found in many other enhancer elements. These results strongly suggest that the two nuclear factors found in hepatoma cells play key roles in the function of the HBV enhancer.