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.

[1]  K. Koike,et al.  Hepatitis B virus X gene expression is activated by X protein but repressed by p53 tumor suppressor gene product in the transient expression system. , 1996, Virology.

[2]  Robert Tjian,et al.  Multiple TAFIIs Directing Synergistic Activation of Transcription , 1995, Science.

[3]  F. Sladek,et al.  Exclusive homodimerization of the orphan receptor hepatocyte nuclear factor 4 defines a new subclass of nuclear receptors , 1995, Molecular and cellular biology.

[4]  A. Ori,et al.  Hepatitis B virus enhancer binds and is activated by the Hepatocyte nuclear factor 3. , 1995, Virology.

[5]  Y. Bergman,et al.  A dynamic balance between ARP-1/COUP-TFII, EAR-3/COUP-TFI, and retinoic acid receptor:retinoid X receptor heterodimers regulates Oct-3/4 expression in embryonal carcinoma cells , 1995, Molecular and cellular biology.

[6]  M. Chen,et al.  Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3. , 1994, Virology.

[7]  N. Benvenisty,et al.  Transcriptional regulation of the phosphoenolpyruvate carboxykinase gene by cooperation between hepatic nuclear factors , 1994, Molecular and cellular biology.

[8]  A. Ori,et al.  An NF1 motif plays a central role in hepatitis B virus enhancer. , 1994, Virology.

[9]  J. Burch,et al.  Identification of factor-binding sites in the duck hepatitis B virus enhancer and in vivo effects of enhancer mutations , 1994, Journal of virology.

[10]  C. Ucla,et al.  RFX1, a transactivator of hepatitis B virus enhancer I, belongs to a novel family of homodimeric and heterodimeric DNA-binding proteins , 1994, Molecular and cellular biology.

[11]  K. Yamamura,et al.  Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors. Both HNF-4 and C/EBP beta are required for liver-specific activity of the ornithine transcarbamylase enhancer. , 1994, The Journal of biological chemistry.

[12]  F. Sladek,et al.  Orphan receptor HNF-4 and bZip protein C/EBP alpha bind to overlapping regions of the apolipoprotein B gene promoter and synergistically activate transcription. , 1993, The Journal of biological chemistry.

[13]  P. Hearing,et al.  Functional interaction of nuclear factors EF-C, HNF-4, and RXR alpha with hepatitis B virus enhancer I , 1993, Journal of virology.

[14]  M. Zakin,et al.  Liver‐enriched HNF‐3α and ubiquitous factors interact with the human transferrin gene enhancer , 1993 .

[15]  K. Koike,et al.  A transcription initiation site for the hepatitis B virus X gene is directed by the promoter-binding protein , 1993, Journal of virology.

[16]  D. Jackson,et al.  Modulation of liver-specific transcription by interactions between hepatocyte nuclear factor 3 and nuclear factor 1 binding DNA in close apposition , 1993, Molecular and cellular biology.

[17]  A. Kahn,et al.  Competition between transcription factors HNF1 and HNF3, and alternative cell-specific activation by DBP and C/EBP contribute to the regulation of the liver-specific aldolase B promoter. , 1993, Nucleic acids research.

[18]  C. Yuh,et al.  Differentiated liver cell specificity of the second enhancer of hepatitis B virus , 1993, Journal of virology.

[19]  K. Koike,et al.  Identification of a binding protein to the X gene promoter region of hepatitis B virus. , 1992, Virology.

[20]  A. Siddiqui,et al.  Retinoid X receptor RXR alpha binds to and trans-activates the hepatitis B virus enhancer. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[21]  K. Umesono,et al.  Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors , 1992, Nature.

[22]  C. Yuh,et al.  Transcriptional regulation of precore and pregenomic RNAs of hepatitis B virus , 1992, Journal of virology.

[23]  J. Yee,et al.  Regulation of hepatitis B virus gene expression by its two enhancers. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[24]  G. Ginsburg,et al.  Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells , 1992, Molecular and cellular biology.

[25]  R. Evans,et al.  Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. , 1992, Genes & development.

[26]  K. Umesono,et al.  Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[27]  A. Kahn,et al.  Interplay of an original combination of factors: C/EBP, NFY, HNF3, and HNF1 in the rat aldolase B gene promoter. , 1991, Nucleic acids research.

[28]  K. Umesono,et al.  A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR , 1991, Cell.

[29]  A. Siddiqui,et al.  Functional analysis of a liver-specific enhancer of the hepatitis B virus. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Darnell,et al.  Hepatocyte nuclear factor 3 alpha belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head. , 1991, Genes & development.

[31]  J. Darnell,et al.  Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. , 1990, Genes & development.

[32]  C. Yuh,et al.  The genome of hepatitis B virus contains a second enhancer: cooperation of two elements within this enhancer is required for its function , 1990, Journal of virology.

[33]  J. Darnell,et al.  HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally. , 1990, Genes & development.

[34]  R. Chalkley,et al.  Interaction of a liver-specific factor with an enhancer 4.8 kilobases upstream of the phosphoenolpyruvate carboxykinase gene , 1990, Molecular and cellular biology.

[35]  Y. Shaul,et al.  Functional organization of the hepatitis B virus enhancer , 1990, Molecular and cellular biology.

[36]  A. Siddiqui,et al.  Multiple liver-specific factors bind to the hepatitis B virus core/pregenomic promoter: trans-activation and repression by CCAAT/enhancer binding protein. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Y. Shaul,et al.  A single element within the hepatitis B virus enhancer binds multiple proteins and responds to multiple stimuli , 1990, Journal of virology.

[38]  A. Siddiqui,et al.  Interactions between nuclear factors and the hepatitis B virus enhancer , 1989, Journal of virology.

[39]  J. Yee.  A liver-specific enhancer in the core promoter region of human hepatitis B virus. , 1989, Science.

[40]  P. Hearing,et al.  Binding of nuclear factor EF-C to a functional domain of the hepatitis B virus enhancer region , 1989, Molecular and cellular biology.

[41]  Y. Shaul,et al.  Cellular factors that interact with the hepatitis B virus enhancer , 1989, Molecular and cellular biology.

[42]  J E Darnell,et al.  Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and alpha 1-antitrypsin genes , 1989, Molecular and cellular biology.

[43]  W. Rutter,et al.  Hepatitis B virus (HBV) promoters are regulated by the HBV enhancer in a tissue-specific manner , 1989, Journal of virology.

[44]  R. Cortese,et al.  Two different liver‐specific factors stimulate in vitro transcription from the human alpha 1‐antitrypsin promoter. , 1988, The EMBO journal.

[45]  I. Dawid,et al.  Purification and properties of Drosophila heat shock activator protein. , 1987, Science.

[46]  K. Koike,et al.  Hepatitis B virus (HBV) particles are produced in a cell culture system by transient expression of transfected HBV DNA. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[47]  A. Siddiqui,et al.  Expression of hepatitis B viral core region in mammalian cells , 1986, Molecular and cellular biology.

[48]  A. Siddiqui,et al.  The human hepatitis B virus enhancer requires trans-acting cellular factor(s) for activity , 1986, Molecular and cellular biology.

[49]  W. Schaffner,et al.  A novel expression selection approach allows precise mapping of the hepatitis B virus enhancer. , 1985, Nucleic acids research.

[50]  W. Rutter,et al.  A human hepatitis B viral enhancer element. , 1985, The EMBO journal.

[51]  M. Yaniv,et al.  Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma , 1984, Cell.

[52]  K. Koike,et al.  Complete nucleotide sequence of hepatitis B virus DNA of subtype adr and its conserved gene organization. , 1984, Gene.

[53]  R. Roeder,et al.  Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. , 1983, Nucleic acids research.

[54]  B. Howard,et al.  Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells , 1982, Molecular and cellular biology.

[55]  Lu-Yu Hwang,et al.  HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUS A Prospective Study of 22 707 Men in Taiwan , 1981, The Lancet.

[56]  G. Vyas,et al.  Biology of hepatitis B virus. , 1981, Science.

[57]  A. van der Eb,et al.  A new technique for the assay of infectivity of human adenovirus 5 DNA. , 1973, Virology.

[58]  Y. Wang,et al.  Transcriptional regulation of the apoAI gene by hepatic nuclear factor 4 in yeast. , 1994, Nucleic acids research.

[59]  A. Siddiqui,et al.  Retinoid X Receptor a Transactivates the Hepatitis B Virus Enhancer 1 Element by Forming a Heterodimeric Complex with the Peroxisome Proliferator-Activated Receptor , 1994 .

[60]  M. Fischer,et al.  Transcriptional control of hepadnavirus gene expression. , 1991, Current topics in microbiology and immunology.

[61]  H. Varmus,et al.  The molecular biology of the hepatitis B viruses. , 1987, Annual review of biochemistry.