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Structure and chromosomal localization of the mouse oncomodulin gene

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Abstract

The rat gene encoding oncomodulin (OM), a small calcium-binding protein, is under the control of a solo LTR derived from an endogenous intracisternal A-particle. The latter sequence is the only OM promoter analyzed so far. In order to study cell-type-specific OM expression in a species lacking LTR sequences in the OM locus, we initially synthesized an OM cDNA from mouse placenta. By sequencing, we found a 137-bp-long 5′ leader region that differed markedly from its rat counterpart but had high similarity to several mouse genomic sequences. Primers specific to this sequence in addition with primers specific for an exon 2/intron 2 sequence were used to screen a mouse ES cell line genomic P1 library. One positive clone contained the whole OM gene, including intron 1 of 25 kb and a 5′ flanking region of 27 kb lacking an LTR. The region upstream of exon 1 contains no TATA or CCAAT boxes but has a homopurine/homopyrimidine stretch of 102 bp as well as a (CA)22 repeat. The latter sequence is polymorphic and was therefore, used to map the OM gene to the distal end of the long arm of mouse Chromosome (Chr) 5 by interspecific backcross analysis. Additonally we localized the OM gene by in situ hybridization to the region G1-3 on Chr 5, confirming the genetic linkage results. Finally, the OM gene was found to be structurally conserved and to exist in a single copy in mammals.

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References

  • Aizawa, H., Sekine, Y., Takemura, R., Zhang, Z., Nangaku, M., Hirokawa, N. (1992). Kinesin family in murine central nervous system. J. Cell Biol. 119, 1287–1296.

    Google Scholar 

  • Banville, D., Boie, Y. (1989). Retroviral long terminal repeat is the promoter of the gene encoding the tumor-associated calcium-binding protein oncomodulin in the rat. J. Mol. Biol. 207, 481–490.

    Google Scholar 

  • Banville, D., Rotaru, M., Boie, Y. (1992). The intracisternal A particle derived solo LTR promoter of the rat oncomodulin gene is not present in the mouse gene. Genetica 86, 85–97.

    Google Scholar 

  • Berchtold, M.W. (1989a). Structure and expression of genes encoding the three-domain Ca2+-binding proteins parvalbumin and oncomodulin. Biochim. Biophys. Acta 1009, 201–215.

    Google Scholar 

  • Berchtold, M.W. (1989b). Parvalbumin genes from human and rat are identical in intron/exon organization and contain highly homologous regulatory elements and coding sequences. J. Mol. Biol. 210, 417–427.

    Google Scholar 

  • Berchtold, M.W., Epstein, P., Beaudet, A.L., Payne, M.E., Heizmann, C.W., Means, A.R. (1987). Structural organization and chromosomal assignment of the parvalbumin gene. J. Biol. Chem. 262, 8696–8701.

    Google Scholar 

  • Biggin, M.D., Tjian, R. (1988). Transcription factors that activate the Ultrabithorax promoter in developmentally staged extracts. Cell 53, 699–711.

    Google Scholar 

  • Biggin, M.D., Tjian, R. (1989). Transcription factors and the control of Drosophila development. Trends Genet 5, 377–383.

    Google Scholar 

  • Breen, M., et al. (1994). Towards high resolution maps of the mouse and human genomes—a facility for ordering markers to 0.1 cM resolution. Hum. Mol. Genet. 3, 621–627.

    Google Scholar 

  • Brewer, L.M., MacManus, J.P. (1985). Localization and synthesis of the tumor protein oncomodulin in extraembryonic tissues of the fetal rat. Dev. Biol. 112, 49–58.

    Google Scholar 

  • Brewer, L.M., MacManus, J.P. (1987). Detection of oncomodulin, an oncodevelopmental protein in human placenta and choriocarcinoma cell lines. Placenta 8, 351–363.

    Google Scholar 

  • Brewer, L.M., Gillen, M.F., MacManus, J.P. (1989). Localization of mRNA for the oncotrophoblastic protein oncomodulin during implantation and early placentation in the rat. Placenta 10, 359–375.

    Google Scholar 

  • Catzeflis, F.M., Dickerman, A.W., Michaux, J., Kirsch, J.A.W. (1993). DNA hybridization and rodent phylogeny. In Mammal Phylogeny, F.S. Szalay, M.J. Novacek, M.C. McKenna, eds. (New York: Springer-Verlag), vol. 2, pp. 159–172.

    Google Scholar 

  • Durkin, J.P., Brewer, L.M., MacManus, J.P. (1983). Occurrence of the tumor-specific, calcium-binding protein, oncomodulin, in virally transformed normal rat kidney cells. Cancer Res. 43, 5390–5394.

    Google Scholar 

  • Feinberg, A.P., Vogelstein, B. (1983). A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6–13.

    Google Scholar 

  • Föhr, U.G., Weber, B.R., Müntener, M., Staudenmann, W., Hughes, G.J., Frutiger, S., Banville, D., Schäfer, B.W., Heizmann, C.W. (1993). Human α and β parvalbumins, structure and tissue-specific expression. Eur. J. Biochem. 215, 719–727.

    Google Scholar 

  • Frischauf, A.-M., Lehrach, H., Poustka, A., Murray, N. (1983). Lambda replacement vectors carrying polylinker sequences. J. Mol. Biol. 170, 827–842.

    Google Scholar 

  • Gillen, M.F., Banville, D., Rutledge, R.G., Narang, S., Seligy, V.L., Whitfield, J.F., MacManus, J.P. (1987). A complete complementary DNA for the oncodevelopmental calcium-binding protein, oncomodulin. J. Biol. Chem. 262, 5308–5312.

    Google Scholar 

  • Hamada, H., Seidman, M., Howard, B.H., Gorman, C.M. (1984). Enhanced gene expression by the poly(dT-dG) poly(dC-dA) sequence. Mol. Cell. Biol. 4, 2622–2630.

    Google Scholar 

  • Hapak, R.C., Zhao, H., Boschi, J.M., Henzl, M.T. (1994). Novel avian thymic parvalbumin displays high degree of sequence homology to oncomodulin. J. Biol. Chem. 269, 5288–5296.

    Google Scholar 

  • Hoffman, K., Trusko, S.P., Murphy, M., George, D.L. (1990). S1 nuclease-sensitive homopurine/homopyrimidine domain in c-Ki-ras promoter interacts with a nuclear factor. Proc. Natl. Acad. Sci. USA 87, 2705–2709.

    Google Scholar 

  • Johnson, A.C., Ishii, S., Jinno, Y., Pastan, I., Merlino, G.T. (1988a). Epidermal growth factor receptor gene promoter. J. Biol. Chem. 263, 5693–5699.

    Google Scholar 

  • Johnson, A.C., Jinno, Y., Merlino, G.T. (1988b). Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease. Mol. Cell. Biol. 8, 4174–4184.

    Google Scholar 

  • Kanungo, J., Pandey, K.N. (1993). Kinasing PCR products for efficient blut-end cloning and linker ligation. Bio Techniques 14, 912–913.

    Google Scholar 

  • Kretsinger, R.H. (1980). Structure and evolution of calcium-modulated proteins. CRC Crit. Rev. Biochem. 8, 119–174.

    Google Scholar 

  • Kuff, E.L., Lueders, K.K. (1988). The intracisternal A-particle gene family: structure and functional aspects. Adv. Cancer Res. 51, 183–276.

    Google Scholar 

  • Lichter, P., Tang, C-JC., Call, K., Hermanson, G., Evans, G.A., Housman, G., Ward, D.C. (1990). High resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 247, 64–69.

    Google Scholar 

  • Lueders, K.K., Kuff, E.L. (1983). Comparison of the sequence organization of related retrovirus-like multigene families in the evolutionary distant rodent genomes. Nucleic Acids Res. 11, 4391–4408.

    Google Scholar 

  • MacManus, J.P., Whitfield, J.F. (1983). Oncomodulin—a calcium-binding protein from hepatoma. In Calcium and Cell Function, W.Y. Cheung, ed. (New York: Academic Press), vol. 4, pp. 412–440.

    Google Scholar 

  • MacManus, J.P., Whitfield, J.F., Stewart, D.J. (1984). The presence in human tumors of a Mr 11700 calcium-binding protein similar to rodent oncomodulin. Cancer Lett. 21, 309–315.

    Google Scholar 

  • MacManus, J.P., Brewer, L.M., Gillen, M.F. (1988). Comparative studies on oncomodulin. In Calcium and Calcium Binding Proteins, C. Gerday, L. Bolis, R. Gilles, eds. (New York: Springer Verlag), pp. 128–138.

    Google Scholar 

  • MacManus, J.P., Brewer, L.M., Banville, D. (1990). Oncomodulin in normal and transformed cells. Adv. Exp. Med. Biol. 269, 107–110.

    Google Scholar 

  • Mavrothalassites, G.J., Watson, D.K., Papas, T.S. (1990). Molecular and functional characterization of the promoter of ETS2, the human c-ets-2 gene. Proc. Natl. Acad. Sci. USA 87, 1047–1051.

    Google Scholar 

  • Ohshima, Y., Gotoh, Y. (1987). Signals for the selection of a splice site in pre-mRNA. J. Mol. Biol. 195, 247–259.

    Google Scholar 

  • Pestov, D.G., Dayn, A., Siyanova, E.Y., George, D.L., Mirkin, S.M. (1991). H-DNA and Z-DNA in the mouse c-Ki-ras promoter. Nucleic Acids Res. 19, 6527–6532.

    Google Scholar 

  • Pierce, J.P., Sternberg, N.L. (1992). Using bacteriophage P1 system to clone high molecular weight genomic DNA. Methods Enzymol. 216, 549–574.

    Google Scholar 

  • Rentsch, J.M. (1994). Cell-type specific acgivity of the rat oncomodulin LTR promoter as revealed in vivo footprinting. Inaugural-Dissertation (Hartung-Gorre Verlag, Konstanz), ISBN 3-89191-811-9.

  • Ritzler, J.M., Sawhney, R., Geurts van Kessel, H.M., Grzeschik, K-H., Schinzel, A., Berchtold, M.W. (1992). The genes for the highly homologous Ca2+-binding proteins oncomodulin and parvalbumin are not linked in the human genome. Genomics 12, 567–572.

    Google Scholar 

  • Said, K., Jacquirt, T., Montgelard, C., Sonjaya, H., Helal, H.N., Britton-Davidian, J. (1986). Robertsonian house mouse population in Tunisia: a karyological and biochemical study. Genetica 68, 151–156.

    Google Scholar 

  • Sambrook, J., Fritsch, E.F., Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, 2nd ed. (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press).

    Google Scholar 

  • Sanger, F., Nicklen, S., Coulson, A.R. (1977). DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA 74, 5463–5467.

    Google Scholar 

  • Santra, M., Danielson, K.G., Iozzo, R.V. (1994). Structural and functional characterization of the human decorin promoter. J. Biol. Chem. 269, 579–587.

    Google Scholar 

  • Schleef, T., Zühlke, C., Jockusch, H., Schöffl, F. (1992). The structure of the mouse parvalbumin gene. Mamm. Genome 3, 217–225.

    Google Scholar 

  • Shirasawa, T., Ohnishi, K., Hagiwara, S., Shigemoto, K., Takebe, Y., Rajewski, K., Takemori, T. (1993). A novel gene product associated with μ chains in immature B cells. EMBO J 12, 1827–1834.

    Google Scholar 

  • Stallings, R.L., Ford, A.F., Nelson, D., Torney, D.C., Hildebrand, C.E., Moyzis, R.K. (1991). Evolution and distribution of (GT)n repetitive sequences in mammalian genomes. Genomics 10, 807–815.

    Google Scholar 

  • Wang, K., Koop, B.F., Hood, L. (1994). A simple method using T4 DNA polymerase to clone PCR products. BioTechniques 17, 236–238.

    Google Scholar 

  • Zörnig, M., Klett, C., Lovec, H., Hameister, H., Winking, H., Adolph, S., Möröy, T. (1995). Establishment of permanent wild-mouse cell lines with readily identifiable marker chromosomes. Cytogenet. Cell Genet., in press.

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Author notes

  1. A. Klein

    Present address: G. Streuli & Co. AG, Städtchen 5, CH-8730, Uznach, Switzerland

  2. J. M. Rentsch

    Present address: Department of Research, Pharmaceutical Division, Ciba-Geigy Ltd., CH-4002, Basel, Switzerland

Authors and Affiliations

  1. Institute of Veterinary Biochemistry, University of Zurich-Irchel, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland

    F. Staubli, A. Klein, J. M. Rentsch & M. W. Berchtold

  2. Department of Medical Genetics, Clinic, University of Ulm, D-89069, Ulm, Germany

    H. Hameister

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  1. F. Staubli
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  5. M. W. Berchtold
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Staubli, F., Klein, A., Rentsch, J.M. et al. Structure and chromosomal localization of the mouse oncomodulin gene. Mammalian Genome 6, 769–777 (1995). https://doi.org/10.1007/BF00539001

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  • DOI: https://doi.org/10.1007/BF00539001

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