Characterization of a specific region in the hepatitis B virus enhancer I for the efficient expression of X gene in the hepatic cell.
Hepatitis B virus (HBV) enhancer I has been shown to consist of several cis-acting sequences for the HBV gene expression efficiently in certain types of cells. Transcriptional regulation of HBV X gene mediated by enhancer I might be one of the mechanisms by which HBV obtains hepatotropism. By mutagenesis analysis of enhancer I function in the enhancer I/X gene promoter complex, we characterized a specific transcriptional regulatory region (designated as a LSR element, nt 989-1030) of enhancer I for the X gene promoter by means of the transient transfection technique using hepatic and nonhepatic cells. Based on the analysis of protein factors interacting with the LSR element, liver-enriched transcriptional factors, HNF3 and HNF4 or retinoid X receptor alpha (RXR alpha), are probably implicated in the activity of enhancer I for the efficient expression of X gene through their interaction with the LSR element in the hepatic cell. Furthermore, the isolated LSR element was demonstrated to function alone as a specific cis-acting element and to be able to activate transcription from the X gene promoter efficiently in the hepatic cell in an orientation-independent manner.
Fukai
K
K
Department of Gene Research, Cancer Institute, JFCR, Tokyo, Japan.
Takada
S
S
Yokosuka
O
O
Saisho
H
H
Omata
M
M
Koike
K
K
D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D015342:DNA Probes / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008099:Liver / Q000821:virology; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015342:DNA Probes; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D010750:Phosphoproteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein