HNF1 is critical for the liver-specific function of HBV enhancer II.

Hepatitis B virus (HBV) is a hepatotropic virus and its gene expression is highly liver-specific. It has been reported that the function of enhancer II (ENII) and the core and the core promoter (Cp) of HBV has a hepatocyte preference. To understand the effects of liver-specific nuclear factors on ENII, in this report, hepatocyte nuclear factor 1 (HNF1) was investigated for its possible action on ENII function. It was found that HNF1 transactivates ENII/Cp in HeLa cells, and antisense HNF1 suppresses it in HepG2 cells. Deletion analysis revealed that the B element of ENII is the target region responsible for the regulation of HNF1. Sequence alignment suggested the presence of the potential HNF1 binding sites in the B element of ENII. The results of electrophoresis mobility shift assay indicated that the B2 region could specifically bind a GST-HNF1 fusion protein and could compete with binding of HNF1 to the consensus motif in the rat beta-fibrinogen promoter, suggesting that the major binding site of HNF1 is located in the B2 region. Our results demonstrate that HNF1 is one of the important regulatory factors for the liver-specific function of HBV and that it transregulates ENII activity via direct binding to B2.