FUNCTIONAL-ANALYSIS OF GROUND-SQUIRREL HEPATITIS-VIRUS ENHANCER-II

We have characterized a major regulatory element of ground squirrel he patitis virus (GSHV) located within a 90-nucleotide fragment of the co re promoter upstream sequences and have compared its organization to t hat of woodchuck hepatitis virus (WHV) enhancer II (We2). The GSHV ele ment (Ge2) stimulates transcription from the viral core promoter and h eterologous promoters in an orientation-independent manner hut display s a lower level of activity than We2 in transient transfection assays in human hepatoma cells, The general organization of Ge2 into binding sites for the liver-enriched HNF-1 and HNF-4 proteins and for ubiquito us factors of the NF1 and Oct families was found to be mostly conserve d with respect to the homologous We2 region, Accordingly, transactivat ion by HNF-1 and HNF-4 plays an essential role in the liver specific t ranscriptional activity of both the GSHV and WHV core promoters, Disti nctive features of the GSHV enhancer consist of its ability to bind C/ EBP family factors in a central motif that overlaps with one of the tw o HNF-4 sites and its differential binding affinities for HNF-4.