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. 1993 Sep;13(9):5854–5860. doi: 10.1128/mcb.13.9.5854

Functionally distinct elements are required for expression of the AMPD1 gene in myocytes.

T Morisaki 1, E W Holmes 1
PMCID: PMC360332  PMID: 8355716

Abstract

AMP deaminase (AMPD) is an enzyme found in all eukaryotic cells. Tissue-specific and stage-specific isoforms of this enzyme are found in vertebrates, and expression of these different isoforms is determined by selective expression of the multiple genes. The AMPD1 gene is expressed predominantly in skeletal muscle, in which transcript abundance is controlled by stage-specific and fiber type-specific signals. This enzyme activity is presumed to be important in skeletal muscle because a metabolic myopathy develops in individuals with an inherited deficiency of AMPD1. In the present study, cis- and trans-acting factors that control expression of AMPD1 have been identified. Two cis-acting elements located within 100 nucleotides of the transcriptional start site are required for muscle-specific expression of AMPD1. One element (-100 to -79) behaves like a tissue-specific enhancer, and it interacts with protein(s) found predominantly in nuclei of myoblasts and myotubes. This element is similar in sequence to an MEF2 binding motif, and it contains an A/T core that is essential for enhancer activity and binding of a nuclear protein(s). The second element (-60 to -40) has properties of a stage-specific promoter in that it is essential for muscle-specific expression of the AMPD1 promoter, does not confer muscle-specific expression on a heterologous promoter construct, and interacts with a protein(s) restricted to nuclei of differentiated myotubes. Interaction between these functionally distinct elements may be required for regulating the expression of AMPD1 during myocyte differentiation and in different muscle fiber types.

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Selected References

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  1. Bausch-Jurken M. T., Mahnke-Zizelman D. K., Morisaki T., Sabina R. L. Molecular cloning of AMP deaminase isoform L. Sequence and bacterial expression of human AMPD2 cDNA. J Biol Chem. 1992 Nov 5;267(31):22407–22413. [PubMed] [Google Scholar]
  2. Buskin J. N., Hauschka S. D. Identification of a myocyte nuclear factor that binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene. Mol Cell Biol. 1989 Jun;9(6):2627–2640. doi: 10.1128/mcb.9.6.2627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cobianchi F., Wilson S. H. Enzymes for modifying and labeling DNA and RNA. Methods Enzymol. 1987;152:94–110. doi: 10.1016/0076-6879(87)52013-4. [DOI] [PubMed] [Google Scholar]
  4. Cserjesi P., Olson E. N. Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products. Mol Cell Biol. 1991 Oct;11(10):4854–4862. doi: 10.1128/mcb.11.10.4854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Felgner P. L., Gadek T. R., Holm M., Roman R., Chan H. W., Wenz M., Northrop J. P., Ringold G. M., Danielsen M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7413–7417. doi: 10.1073/pnas.84.21.7413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gossett L. A., Kelvin D. J., Sternberg E. A., Olson E. N. A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Mol Cell Biol. 1989 Nov;9(11):5022–5033. doi: 10.1128/mcb.9.11.5022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gunning P., Leavitt J., Muscat G., Ng S. Y., Kedes L. A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831–4835. doi: 10.1073/pnas.84.14.4831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gustafson T. A., Kedes L. Identification of multiple proteins that interact with functional regions of the human cardiac alpha-actin promoter. Mol Cell Biol. 1989 Aug;9(8):3269–3283. doi: 10.1128/mcb.9.8.3269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hall C. V., Jacob P. E., Ringold G. M., Lee F. Expression and regulation of Escherichia coli lacZ gene fusions in mammalian cells. J Mol Appl Genet. 1983;2(1):101–109. [PubMed] [Google Scholar]
  11. Hobson G. M., Mitchell M. T., Molloy G. R., Pearson M. L., Benfield P. A. Identification of a novel TA-rich DNA binding protein that recognizes a TATA sequence within the brain creatine kinase promoter. Nucleic Acids Res. 1988 Sep 26;16(18):8925–8944. doi: 10.1093/nar/16.18.8925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Horlick R. A., Benfield P. A. The upstream muscle-specific enhancer of the rat muscle creatine kinase gene is composed of multiple elements. Mol Cell Biol. 1989 Jun;9(6):2396–2413. doi: 10.1128/mcb.9.6.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Krieg P. A., Melton D. A. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. doi: 10.1016/0076-6879(87)55027-3. [DOI] [PubMed] [Google Scholar]
  14. Li Z. L., Paulin D. High level desmin expression depends on a muscle-specific enhancer. J Biol Chem. 1991 Apr 5;266(10):6562–6570. [PubMed] [Google Scholar]
  15. Mahdavi V., Chambers A. P., Nadal-Ginard B. Cardiac alpha- and beta-myosin heavy chain genes are organized in tandem. Proc Natl Acad Sci U S A. 1984 May;81(9):2626–2630. doi: 10.1073/pnas.81.9.2626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mahnke-Zizelman D. K., Sabina R. L. Cloning of human AMP deaminase isoform E cDNAs. Evidence for a third AMPD gene exhibiting alternatively spliced 5'-exons. J Biol Chem. 1992 Oct 15;267(29):20866–20877. [PubMed] [Google Scholar]
  17. Mar J. H., Ordahl C. P. A conserved CATTCCT motif is required for skeletal muscle-specific activity of the cardiac troponin T gene promoter. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6404–6408. doi: 10.1073/pnas.85.17.6404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marquetant R., Desai N. M., Sabina R. L., Holmes E. W. Evidence for sequential expression of multiple AMP deaminase isoforms during skeletal muscle development. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2345–2349. doi: 10.1073/pnas.84.8.2345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Meyer S. L., Kvalnes-Krick K. L., Schramm V. L. Characterization of AMD, the AMP deaminase gene in yeast. Production of amd strain, cloning, nucleotide sequence, and properties of the protein. Biochemistry. 1989 Oct 31;28(22):8734–8743. doi: 10.1021/bi00448a009. [DOI] [PubMed] [Google Scholar]
  20. Mineo I., Clarke P. R., Sabina R. L., Holmes E. W. A novel pathway for alternative splicing: identification of an RNA intermediate that generates an alternative 5' splice donor site not present in the primary transcript of AMPD1. Mol Cell Biol. 1990 Oct;10(10):5271–5278. doi: 10.1128/mcb.10.10.5271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Montarras D., Pinset C., Chelly J., Kahn A., Gros F. Expression of MyoD1 coincides with terminal differentiation in determined but inducible muscle cells. EMBO J. 1989 Aug;8(8):2203–2207. doi: 10.1002/j.1460-2075.1989.tb08343.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Morisaki T., Gross M., Morisaki H., Pongratz D., Zöllner N., Holmes E. W. Molecular basis of AMP deaminase deficiency in skeletal muscle. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6457–6461. doi: 10.1073/pnas.89.14.6457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Morisaki T., Sabina R. L., Holmes E. W. Adenylate deaminase. A multigene family in humans and rats. J Biol Chem. 1990 Jul 15;265(20):11482–11486. [PubMed] [Google Scholar]
  24. Nudel U., Calvo J. M., Shani M., Levy Z. The nucleotide sequence of a rat myosin light chain 2 gene. Nucleic Acids Res. 1984 Sep 25;12(18):7175–7186. doi: 10.1093/nar/12.18.7175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ogasawara N., Goto H., Yamada Y., Watanabe T. Distribution of AMP-deaminase isozymes in rat tissues. Eur J Biochem. 1978 Jun 15;87(2):297–304. doi: 10.1111/j.1432-1033.1978.tb12378.x. [DOI] [PubMed] [Google Scholar]
  26. Pollock R., Treisman R. Human SRF-related proteins: DNA-binding properties and potential regulatory targets. Genes Dev. 1991 Dec;5(12A):2327–2341. doi: 10.1101/gad.5.12a.2327. [DOI] [PubMed] [Google Scholar]
  27. Pugh B. F., Tjian R. Mechanism of transcriptional activation by Sp1: evidence for coactivators. Cell. 1990 Jun 29;61(7):1187–1197. doi: 10.1016/0092-8674(90)90683-6. [DOI] [PubMed] [Google Scholar]
  28. Sabina R. L., Morisaki T., Clarke P., Eddy R., Shows T. B., Morton C. C., Holmes E. W. Characterization of the human and rat myoadenylate deaminase genes. J Biol Chem. 1990 Jun 5;265(16):9423–9433. [PubMed] [Google Scholar]
  29. Sabina R. L., Ogasawara N., Holmes E. W. Expression of three stage-specific transcripts of AMP deaminase during myogenesis. Mol Cell Biol. 1989 May;9(5):2244–2246. doi: 10.1128/mcb.9.5.2244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Selden R. F., Howie K. B., Rowe M. E., Goodman H. M., Moore D. D. Human growth hormone as a reporter gene in regulation studies employing transient gene expression. Mol Cell Biol. 1986 Sep;6(9):3173–3179. doi: 10.1128/mcb.6.9.3173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  32. Takahashi K., Vigneron M., Matthes H., Wildeman A., Zenke M., Chambon P. Requirement of stereospecific alignments for initiation from the simian virus 40 early promoter. Nature. 1986 Jan 9;319(6049):121–126. doi: 10.1038/319121a0. [DOI] [PubMed] [Google Scholar]
  33. Walsh K. Cross-binding of factors to functionally different promoter elements in c-fos and skeletal actin genes. Mol Cell Biol. 1989 May;9(5):2191–2201. doi: 10.1128/mcb.9.5.2191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yu Y. T., Breitbart R. E., Smoot L. B., Lee Y., Mahdavi V., Nadal-Ginard B. Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. Genes Dev. 1992 Sep;6(9):1783–1798. doi: 10.1101/gad.6.9.1783. [DOI] [PubMed] [Google Scholar]
  35. Zakut R., Shani M., Givol D., Neuman S., Yaffe D., Nudel U. Nucleotide sequence of the rat skeletal muscle actin gene. Nature. 1982 Aug 26;298(5877):857–859. doi: 10.1038/298857a0. [DOI] [PubMed] [Google Scholar]

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