Retrovirus activation in embryonal carcinoma cells by cellular promoters.

Retrovirus expression in embryonal carcinoma (EC) cells is blocked at a postintegration stage of the viral life cycle, because of the inadequate function of the viral long terminal repeat (LTR) promoter in this cell type. However, rare sites in the EC cell genome permit provirus expression by undefined mechanisms. Our analysis of three expressed proviruses indicates that they have inserted into actively transcribed regions. Two of the three, examined in detail, integrated into the first introns of cellular transcription units in close proximity to active cellular promoters. One of these cellular genes is the probable murine homolog of the yeast ribosomal protein L3, responsible for trichodermin resistance. In all cases, virus activation appears to involve production of viral transcripts that are initiated in the 5'-flanking region, transcribed through the viral LTR, and subsequently spliced from a cellular donor to a viral acceptor. Our results suggest a general procedure for the isolation of active genes and promoters in different tissues.

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

[2]  M. Taketo,et al.  Two blocks in Moloney murine leukemia virus expression in undifferentiated F9 embryonal carcinoma cells as determined by transient expression assays , 1989, Journal of virology.

[3]  A. Joyner,et al.  Mouse embryonic stem cells and reporter constructs to detect developmentally regulated genes. , 1989, Science.

[4]  L. Staudt,et al.  Repression of the IgH enhancer in teratocarcinoma cells associated with a novel octamer factor. , 1989, Science.

[5]  J. Yon,et al.  Ribosomal protein L7a is encoded by a gene (Surf-3) within the tightly clustered mouse surfeit locus , 1989, Molecular and cellular biology.

[6]  H. Hamada,et al.  Functional cloning of mouse chromosomal loci specifically active in embryonal carcinoma stem cells , 1988, Molecular and cellular biology.

[7]  J. Sutcliffe,et al.  p1B15: a cDNA clone of the rat mRNA encoding cyclophilin. , 1988, DNA.

[8]  P. Rigby,et al.  Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses. , 1988, Genes & development.

[9]  Robert Tjian,et al.  Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain , 1987, Cell.

[10]  R. Scott,et al.  Proviral sequences that restrict retroviral expression in mouse embryonal carcinoma cells , 1987, Molecular and cellular biology.

[11]  C. Benoist,et al.  A multiplicity of CCAAT box-binding proteins , 1987, Cell.

[12]  R. Jaenisch,et al.  Two distinct sequence elements mediate retroviral gene expression in embryonal carcinoma cells , 1987, Journal of virology.

[13]  C. Stocking,et al.  Functional analysis of a retroviral host-range mutant: altered long terminal repeat sequences allow expression in embryonal carcinoma cells. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Coffin,et al.  Efficient packaging of readthrough RNA in ALV: implications for oncogene transduction. , 1987, Science.

[15]  R. Mulligan,et al.  Regulated expression of a complete human beta-globin gene encoded by a transmissible retrovirus vector , 1987, Molecular and cellular biology.

[16]  T. Doetschman,et al.  Transgenesis by means of blastocyst-derived embryonic stem cell lines. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[17]  R. Jaenisch,et al.  Chromosomal position or virus mutation permits retrovirus expression in embryonal carcinoma cells , 1986, Cell.

[18]  A. Bradley,et al.  Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector , 1986, Nature.

[19]  David Baltimore,et al.  Multiple nuclear factors interact with the immunoglobulin enhancer sequences , 1986, Cell.

[20]  J. Nevins,et al.  Identification of a cellular transcription factor involved in E1A trans-activation , 1986, Cell.

[21]  J. Beckwith,et al.  TnphoA: a transposon probe for protein export signals. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[22]  H. Nam,et al.  Identification of a nuclear localization signal of a yeast ribosomal protein. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[23]  P. Rigby,et al.  Negative regulation of viral enhancers in undifferentiated embryonic stem cells , 1985, Cell.

[24]  H. Lodish,et al.  Structure of the promoter of the Dictyostelium discoideum prespore EB4 gene , 1985, Molecular and cellular biology.

[25]  E. Gilboa,et al.  Isolation of embryonal carcinoma cell lines that express integrated recombinant genes flanked by the Moloney murine leukemia virus long terminal repeat. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. Way,et al.  New Tn10 derivatives for transposon mutagenesis and for construction of lacZ operon fusions by transposition. , 1984, Gene.

[27]  J. Sorge,et al.  Integration-specific retrovirus expression in embryonal carcinoma cells. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D. Melton,et al.  Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. , 1984, Nucleic acids research.

[29]  C. Cepko,et al.  Construction and applications of a highly transmissible murine retrovirus shuttle vector , 1984, Cell.

[30]  S. Henikoff.  Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. , 1984, Gene.

[31]  J. Nevins,et al.  Common control of the heat shock gene and early adenovirus genes: evidence for a cellular E1A-like activity , 1984, Molecular and cellular biology.

[32]  B. A. Castilho,et al.  Plasmid insertion mutagenesis and lac gene fusion with mini-mu bacteriophage transposons , 1984, Journal of bacteriology.

[33]  A. Bradley,et al.  Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines , 1984, Nature.

[34]  J. Friesen,et al.  Nucleotide sequence of the tcml gene (ribosomal protein L3) of Saccharomyces cerevisiae , 1983, Journal of bacteriology.

[35]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[36]  L. Lania,et al.  Isolation of cellular DNA sequences that allow expression of adjacent genes. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[37]  H. Lodish,et al.  Regulation of dictyostelium discoideum mRNAs specific for prespore or prestalk cells , 1983, Cell.

[38]  M. Shani,et al.  The nucleotide sequence of the rat cytoplasmic β–actin gene , 1983 .

[39]  J. Reiser,et al.  Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit β-globin gene in mouse 3T6 cells , 1983, Cell.

[40]  R. Jaenisch,et al.  Germline integration of Moloney murine leukemia virus at the Mov13 locus leads to recessive lethal mutation and early embryonic death , 1983, Cell.

[41]  H. Lodish,et al.  Transcriptional control of gene expression during development of Dictyostelium discoideum , 1982, Molecular and cellular biology.

[42]  R. Jaenisch,et al.  De novo methylation, expression, and infectivity of retroviral genomes introduced into embryonal carcinoma cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Stephen M. Mount,et al.  A catalogue of splice junction sequences. , 1982, Nucleic acids research.

[44]  G. Martin,et al.  Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[45]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[46]  P Chambon,et al.  Promoter sequences of eukaryotic protein-coding genes. , 1980, Science.

[47]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[48]  George R. Stark,et al.  Regulation of Simian Virus 40 Transcription: Sensitive Analysis of the RNA Species Present Early in Infections by Virus or Viral DNA , 1979, Journal of virology.

[49]  J. Darnell,et al.  Production of mRNA in chinese hamster cells: Relationship of the rate of synthesis to the cytoplasmic concentration of nine specific mRNA sequences , 1979, Cell.

[50]  S. Strickland,et al.  The induction of differentiation in teratocarcinoma stem cells by retinoic acid , 1978, Cell.

[51]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[52]  D. Lowy,et al.  Virus infection of murine teratocarcinoma stem cell lines , 1977, Cell.

[53]  W. D. Benton,et al.  Screening lambdagt recombinant clones by hybridization to single plaques in situ. , 1977, Science.

[54]  E. Southern.  Detection of specific sequences among DNA fragments separated by gel electrophoresis. , 1975, Journal of molecular biology.

[55]  B. Ephrussi,et al.  Alkaline phosphatase activity in mouse teratoma. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

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