Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1994-07-15
1997-08-05
Elliott, George C.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
4351723, 4353201, 536 237, 536 241, C12P 2100, C12N 1500, C12N 1563, C07H 2104
Patent
active
056541686
ABSTRACT:
Nucleic acid molecules and proteins useful for regulating the expression of genes in eukaryotic cells and organisms in an inducible manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is stimulated by a transcriptional activator fusion protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences in the presence of tetracycline or a tetracycline analogue and a second polypeptide which directly or indirectly activates transcription in eukaryotic cells. In one embodiment, the fusion protein comprises a mutated Tet repressor operatively linked to a transcriptional activation polypeptide, such as a portion of herpes simplex virus virion protein 16. In the absence of an inducing agent (tetracycline or a tetracycline analogue), transcription of the tet operator-linked nucleotide sequence remains uninduced. In the presence of the inducing agent, transcription of the tet operator-linked nucleotide sequence is stimulated by the transactivator fusion protein of the invention. Novel transcription units which allow for coordinate or independent tetracycline-regulated expression of two or more nucleotide sequences by the transactivator fusion protein of the invention are also disclosed. Kits including the components of the regulatory system of the invention are also encompassed by the invention.
REFERENCES:
patent: 4833080 (1989-05-01), Brent et al.
patent: 5221778 (1993-06-01), Byrne et al.
Gossen, M., "Prokaryontische Repressor/Operatorsysteme in der Kontrolle der eukaryotischen Genexpression" (Inaugural-Dissertation, Universitat Heidelberg), 1993.
Wissmann et al. Selection ofr Tn10 Tet repressor binding to tet operator in Escherichis coli: Isolation of temperature-sensitive mutants and combinatorial mutagenesis in the DNA binding motif Genetics vol. 128 225-232 1991.
Mendez et al. Heterogeneity of tetracycline resistance determinants Plasmid vol. 3 99-108 1980.
Cowell, "Repression versus activation in the control of gene transcription," Trends in Biochemical Sciences, 19:1, 38-42 (1994).
Deuschle et al., "Tetracycline-reversible silencing of eukaryotic promoters," Mol. Cell. Biol., 15:4, 1907-1914 (1995).
Gatz et al., "Stringent repression and homogeneous de-repression by tetracycline of a modified CaMV 35S promoter in intact transgenic tobacco plants," The Plant Journal, 2:3, 397-404 (1992).
Gossen et al., "Exploiting prokaryotic elements for the control of gene activity in higher eukaryotics," Keystone Symposium on Gene Therapy and Molecular Medicine, Steamboat Springs, Colorado, Journal of Cellular Biochemistry, Supplement 0 (21A), Abstract No. C6-220, 355 (1995).
Gossen et al., "Transcriptional activation by tetracyclines in mammalian cells," Science, 268:5218, 1766-1769 (1995).
Liang et al., "Enhanced and switchable expression systems for gene-transfer," Keystone Symposium on Gene Therapy and Molecular Medicine, Steamboat Springs, Colorado, Journal of Cellular Biochemistry, Supplement 0 (21A), Abstract No. C6-220, 379 (1995).
Brent, R. and M. Ptashne (1984) "A Bacterial Repressor Protein or a Yeast Transcriptional Terminator Can Block Upstream Activation of A Yeast Gene" Nature 312:612-615.
Brent R. and M. Ptashne (1985) "A Eukaryotic Transcriptional Activator Bearing the DNA Specificity of a Prokaryotic Repressor" Cell 43:729-736.
Hinrichs, W., et al., (1994) "Structure of the Tet Repressor-Tetracycline Complex and Regulation of Antibiotic Resistance", Science, vol. 264, pp. 418-420.
Hecht, B., et al., (1993) "Noninducible Tet Repressor Mutations Map from the Operator Motif to the C Terminus", Journal of Bacteriology, vol. 175, No. 4.
Gossen, M., et al., (1993) "Control of gene activity in higher eukaryotic cells by prokaryotic regulatory elements", TIBS, vol. 18, No. 12, pp. 471-475.
Fieck, A., et al., (1992) "Modification of the E. coli Lac Repressor for Expression in Eukaryoitic Cells: Effect of Nuclear Signal Sequence on Protein Activity and Nuclear Documentation", Nucleic Acid Research, vol. 20, pp. 1785-1791.
Seipel, K., et al., (1992) "Different activation domains stimulate transcription from remote (`enhancer`) and proximal (`promoter`) positions", The EMBO Journal, vol. 11, No. 13, pp. 4961-4968.
Epstein-Baak, R., et al., (1992) "Inducible Transformation of Cells from Transgenic Mice Expressing SV40 under Lac Operon Control", Cell Growth & Differentiation, vol. 3, pp. 127-134.
Gossen, M., and Bujard, H., (1992) "Tight control of gene expression in mammalian cells by tetracycline-responsive promoters", Proceedings of the National Academy of Science vol. 89, pp. 5547-5551.
Bradley, A., (1991) "Modifying the mammalian genome by gene targeting", Current Opinion in Biotechnology, vol. 2, pp. 832-829.
Wyborski, D.L., and Short, J.M., (1991) "Analysis of Inducers of the E. coli Lac Repressor System in Mammalian Cells and Whole Animals", Nucleic Acid Research, vol. 19, pp. 4647-4653.
Degenkolb, J., et al., (1991) "Structural Requirements of Tetracycline-Tet Repressor Interaction: Determination of Equilibrium Binding Constants for Tetracycline Analogs with the Tet Repressor", Antimicrobial Agents and Chemotherapy, vol. 35, No. 8, pp. 1591-1595.
Baim, S.B., et al., (1991) "A chimeric mammalian transactivator based on the lac repressor that is regulated by temperature and isopropyl .beta.-D-thiogalactopyranoside", Proceedings of the National Academy of Science, vol. 88, pp. 5072-5076.
Gatz, C., et al., (1991) "Regulation of a modified CaMV 35S promoter by the Tn 10-encoder Tet receptor in transgenic tobacco", Mol. Gen. Genet., vol. 227, No. 2, pp. 229-237.
Wissmann, A., et al., (1991) "Selection for Tn10 Tet Repressor Binding to tet Operator in Escherichia coli: Isolation of Temperature-Sensitive Mutants and Combinatorial Mutagenesis in the DNA Binding Motif", Genetics, vol. 128, pp. 225-232.
Labow, M.A., et al., (1990) "Conversion of the lac Repressor into an Allosterically Regulated Transcriptional Activator for Mammalian Cells", Molecular and Cellular Biology, vol. 10, No. 7, pp. 3343-3356.
Deuschle, U., et al., (1989) "Regulated expression of foreign genes in mammalian cells under the control of coliphage T3 RNA polymerase and lac repressor", Proceedings of the National Academy of Science, vol. 86, pp. 5400-5404.
Capecchi, M.R., (1989) "Altering the Genome by Homologous Recombination", Science, vol. 244, pp. 1288-1292.
Mermod, N., et al., (1989), "The Proline-Rich Transcriptional Activator of CTF/NF-I Is Distinct from the Replication and DNA Binding Domain", Cell, vol. 58, 741-753.
Mansour, S.L., et al., (1989) "Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes", Nature, vol. 336, pp. 348-352.
Gatz, C., and Quail, P.H., (1988) "Tn10-encoded tet repressor can regulate an operator-containing plant promoter", Proceedings of the National Academy of Science, vol. 85, pp. 1394-1397.
Figge, J., et al., (1988) "Stringent Regulation of Stably Integrated Chloramphenicol Acetyl Transferase Genes by E. coli lac Repressor in Monkey Cells", Cell, vol. 52, 713-722.
Triezenberg, S.J., et al., (1988) "Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression", Genes & Development, vol. 2, pp. 718-729.
Courey, A.J., and Tijan, R., (1988) "Analysis of Sp1 In Vivo Reveals Multiple Transcriptional Domains, Including a Novel Glutamine-Rich Activation Motif", Cell, vol. 55, pp. 887-898.
Tovar, K., et al., (1988) "Identification and nucleotide sequence of the class E tet regulatory elements and operator and inducer binding of the encoded purified Tet repressor", Mol. Gen. Genet., vol. 215, pp. 76-80.
Altschmied, L. et al., (1988) "A threonine to alanine exchange at position 40 of Tet repressor alters the recognition of the sixth base pair of tet operator from GC to AT", The EMBO Journal, vol. 7, No. 12, pp. 4011-4017.
Brown, M., et al., (1987) "lac Repressor Can Regulate Expression from a Hybrid SV40 Early Promoter Containing a lac Operator in Animal Cells",
Bujard Hermann
Gossen Manfred
BASF - Aktiengesellschaft
Brusca John S.
DeConti, Jr. Giulio A.
Elliott George C.
Knoll Aktiengesellschaft
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