Cellular factors controlling the activity of woodchuck hepatitis virus enhancer II

Woodchuck hepatitis virus (WHV) efficiently induces hepatocellular carcinoma in chronically infected hosts. A key step in hepatocarcinogenesis by WHV is insertional activation of the cellular N-myc gene by integrated viral DNA. WHV enhancer II (En II) is the major cis-acting element involved in this activation. Here we characterize this viral enhancer element and define the cellular factors involved in its activity. WHV En II activity is strongly liver specific and maps to an 88-nucleotide DNA segment (nucleotides 1772 to 1859) located 5' to the pregenomic RNA start site. Genetic analyses and electrophoretic mobility shift assays indicate that the enhancer contains three subregions important to its activity. The core elements of the enhancer are recognition sites for the liver-enriched factors HNF1 and HNF4; together, these signals account for the bulk of En II activity as well as its strong liver specificity. Multimerization of either recognition site produced strong activity even in the absence of other En II sequences. 5' to these elements is a binding site for the ubiquitous Oct-1 transcription factor, which further augments enhancer activity ca. twofold.

[1]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[2]  D. Ganem,et al.  Activation of N-myc2 gene expression by cis-acting elements of oncogenic hepadnaviral genomes: key role of enhancer II. , 1996, Virology.

[3]  J. Johnson,et al.  Characterization of a functional hepatocyte nuclear factor 3 binding site in the hepatitis B virus nucleocapsid promoter. , 1995, Virology.

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

[5]  F. Sladek,et al.  The orphan receptors COUP-TF and HNF-4 serve as accessory factors required for induction of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

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

[7]  G. Fourel,et al.  Evidence for long‐range oncogene activation by hepadnavirus insertion. , 1994, The EMBO journal.

[8]  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.

[9]  G. McKnight,et al.  A C/EBP-binding site in the transferrin promoter is essential for expression in the liver but not the brain of transgenic mice , 1993, Molecular and cellular biology.

[10]  J. Yee,et al.  Mutational analysis of hepatitis B virus enhancer 2. , 1993, Virology.

[11]  B. Durand,et al.  RFX1 is identical to enhancer factor C and functions as a transactivator of the hepatitis B virus enhancer , 1993, Molecular and cellular biology.

[12]  K Tanaka,et al.  Analysis of the rat hepatocyte nuclear factor (HNF) 1 gene promoter: synergistic activation by HNF4 and HNF1 proteins. , 1993, Nucleic acids research.

[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]  T. Yen.  Regulation of hepatitis B virus gene expression , 1993 .

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

[16]  D. Ganem,et al.  Differential activation of myc gene family members in hepatic carcinogenesis by closely related hepatitis B viruses , 1993, Molecular and cellular biology.

[17]  G. Fourel,et al.  Expression of the woodchuck N-myc2 retroposon in brain and in liver tumors is driven by a cryptic N-myc promoter , 1992, Molecular and cellular biology.

[18]  G. Fourel,et al.  Hepadnavirus integration: mechanisms of activation of the N-myc2 retrotransposon in woodchuck liver tumors , 1992, Journal of virology.

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

[20]  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.

[21]  W. Herr,et al.  Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter , 1992, Cell.

[22]  W. Herr,et al.  The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeo domain: evidence for a homeo domain recognition subdomain. , 1991, Genes & development.

[23]  U. Schibler,et al.  A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the sam mRNA , 1991, Cell.

[24]  A. Easton,et al.  Promoter-specific transactivation of hepatitis B virus transcription by a glutamine- and proline-rich domain of hepatocyte nuclear factor 1 , 1991, Journal of virology.

[25]  C. Yuh,et al.  C/EBP-like proteins binding to the functional box-alpha and box-beta of the second enhancer of hepatitis B virus , 1991, Molecular and cellular biology.

[26]  P. Johnson,et al.  A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro. , 1991, Genes & development.

[27]  A. Siddiqui,et al.  Transcriptional factor C/EBP binds to and transactivates the enhancer element II of the hepatitis B virus. , 1991, Virology.

[28]  I. Bach,et al.  Two members of an HNF1 homeoprotein family are expressed in human liver , 1991, Nucleic Acids Res..

[29]  M. Levrero,et al.  Identification of a strong enhancer element upstream from the pregenomic RNA start site of the duck hepatitis B virus genome , 1991, Journal of virology.

[30]  M. Yaniv,et al.  vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1. , 1991, The EMBO journal.

[31]  G. Crabtree,et al.  HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. , 1991, Genes & development.

[32]  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.

[33]  A. Siddiqui,et al.  Regulation of the hepatitis B virus gene expression by the enhancer element I. , 1991, Virology.

[34]  H. Varmus,et al.  Woodchuck hepatitis virus is a more efficient oncogenic agent than ground squirrel hepatitis virus in a common host , 1991, Journal of virology.

[35]  W. Schaffner,et al.  Promoters with the octamer DNA motif (ATGCAAAT) can be ubiquitous or cell type-specific depending on binding affinity of the octamer site and Oct-factor concentration. , 1991, Nucleic acids research.

[36]  G. Crabtree,et al.  HNF-1, a member of a novel class of dimerizing homeodomain proteins. , 1991, The Journal of biological chemistry.

[37]  G. Crabtree,et al.  Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

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

[39]  M. Zakin,et al.  The binding site for the liver-specific transcription factor Tf-LF1 and the TATA box of the human transferrin gene promoter are the only elements necessary to direct liver-specific transcription in vitro. , 1990, Nucleic acids research.

[40]  G. Fourel,et al.  Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours , 1990, Nature.

[41]  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.

[42]  W. Schaffner,et al.  Octamer transcription factors and the cell type‐specificity of immunoglobulin gene expression , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[43]  W. Herr,et al.  Differential transcriptional activation by Oct-1 and Oct-2: Interdependent activation domains induce Oct-2 phosphorylation , 1990, Cell.

[44]  S. McKnight,et al.  Cognate DNA binding specificity retained after leucine zipper exchange between GCN4 and C/EBP. , 1989, Science.

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

[46]  B. Tennant,et al.  Expression of infectious woodchuck hepatitis virus in murine and avian fibroblasts , 1989, Journal of virology.

[47]  R. Cortese,et al.  The liver-specific transcription factor LF-B1 contains a highly diverged homeobox DNA binding domain , 1989, Cell.

[48]  B. O’Malley,et al.  COUP transcription factor is a member of the steroid receptor superfamily , 1989, Nature.

[49]  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.

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

[51]  W. Herr,et al.  The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. , 1988, Genes & development.

[52]  J. Wijnholds,et al.  Tissue‐specific and steroid‐dependent interaction of transcription factors with the oestrogen‐inducible apoVLDL II promoter in vivo. , 1988, The EMBO journal.

[53]  J. Perez-Mutul,et al.  Mutational analysis of the contribution of sequence motifs within the IgH enhancer to tissue specific transcriptional activation , 1988, Nucleic Acids Res..

[54]  S. McKnight,et al.  Isolation of a recombinant copy of the gene encoding C/EBP. , 1988, Genes & development.

[55]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[56]  A. Levinson,et al.  Properties of the human hepatitis B virus enhancer: position effects and cell-type nonspecificity , 1988, Journal of virology.

[57]  P. Galle,et al.  Expression and replication of the hepatitis B virus genome under foreign promoter control. , 1987, Nucleic acids research.

[58]  E. Elfassi.  Broad specificity of the hepatitis B enhancer function. , 1987, Virology.

[59]  B. O’Malley,et al.  Interactions between a DNA-binding transcription factor (COUP) and a non-DNA binding factor (S300-II) , 1987, Cell.

[60]  R. Tjian,et al.  Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements , 1987, Cell.

[61]  R. Purcell,et al.  Hepatocarcinogenicity of the woodchuck hepatitis virus. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[62]  Robert Tjian,et al.  A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication , 1987, Cell.

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

[64]  H. Yoshikawa,et al.  Nucleotide sequence of a cloned woodchuck hepatitis virus genome: evolutional relationship between hepadnaviruses , 1985, Journal of virology.

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

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

[67]  W. Robinson,et al.  Molecular events in the pathogenesis of hepadnavirus-associated hepatocellular carcinoma. , 1994, Annual review of medicine.

[68]  W. Herr,et al.  Differential positive control by Oct-1 and Oct-2: activation of a transcriptionally silent motif through Oct-1 and VP16 corecruitment. , 1993, Genes & development.

[69]  M. Yaniv,et al.  The HNF1 C-terminal domain contributes to transcriptional activity and modulates nuclear localisation. , 1993, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[70]  P. Carlsson,et al.  Two nuclear proteins bind to the major positive element of the apolipoprotein B gene promoter. , 1990, Gene.

[71]  H. Blum,et al.  The molecular biology of hepatitis B virus. , 1989, Trends in genetics : TIG.

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

[73]  W. Rutter,et al.  THE NUCLEOTIDE SEQUENCE OF THE HEPATITIS B VIRAL GENOME AND THE IDENTIFICATION OF THE MAJOR VIRAL GENES , 1980 .