, Volume 31, Issue 5–6, pp 361–367 | Cite as

Post-transcriptional regulation of complement C4 in low C4-producing strain of mouse

  • Kohzo Nakayama
  • Sa-nga Pattanakitsakul
  • Shigeru Yokoyama
  • Masaru Nonaka
  • Morinobu Takahashi
  • Hiroshi Kimura


The expression of the fourth component of complement (C4) of the mouse can differ 20-fold and is determined byC4-high (C4 h ) orC4-low (C4 l ) alleles. To investigate the molecular mechanisms underlying the differences in C4 expression, we compared the transcriptional activity of theC4 genes between high and low C4-producer strains of mice (B10 and FM vs B10.BR) using nuclear transcriptional and chloramphenicol acetyltransferase (CAT) assays. We also compared the level of C4-specific RNA in total and nuclear RNA of the liver. The results revealed no significant difference in transcriptional activity betweenC4 h andC4 l genes. However, the steady-state levels of C4 mRNA are ten times lower inC4 l strains than inC4 h strains, suggesting that the major regulation of C4 plasma levels occurs at the post-transcriptional level.


Molecular Mechanism Plasma Level Transcriptional Activity Chloramphenicol Major Regulation 
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  1. Baldwin, A. S. and Sharp, P. A.: Binding of a nuclear factor to a regulatory sequence in the promoter of the mouse H-2kb class I major histocompatibility gene.Mol Cell Biol 7: 305–313, 1987PubMedGoogle Scholar
  2. Benton, W. D. and Davis, R. W.: Screening λgt recombinant clones by hybridization to single plaques in situ.Science 196: 180–182, 1977PubMedGoogle Scholar
  3. Blin, N. and Stafford, D. W.: A general method for isolation of high molecular weight DNA from eukaryotes.Nucleic Acids Res 3: 2303–2308, 1976PubMedGoogle Scholar
  4. Brewer, G. and Ross, J.: Poly(A) shortening and degradation of the 3′ A+U-rich sequences of human c-myc mRNA in a cell-free system.Mol Cell Biol 8: 1697–1708, 1988PubMedGoogle Scholar
  5. Bruisten, S. M., Demant, P., and Robins, D. M.: Trans-regulatory genes affect Slpa and Slpo expression and act in a tissue-specific manner.Immunogenetics 29: 340–345, 1989PubMedGoogle Scholar
  6. Chaplin, D. D., Woods, D. E., Whitehead, A. S., Goldberger, G., Colten, H. R., and Seidman, J. G.: Molecular map of the murine S region.Proc Natl Acad Sci USA 80: 6947–6951, 1983PubMedGoogle Scholar
  7. Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J., and Rutter, W. J.: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.Biochemistry 18: 5294–5299, 1979PubMedGoogle Scholar
  8. Gigli, I.: A single chain precursor of C4 in human serum.Nature 272: 836–837, 1978PubMedGoogle Scholar
  9. Giros, B., Sokoloff, P., Martres, M.-P., Riou, J.-F., Emorine, L. J., and Schwartz, J.-C.: Alternative splicing directs the expression of two D2 dopamine receptor isoforms.Nature 342: 923–926, 1989PubMedGoogle Scholar
  10. Gorman, C. M., Moffat, L. F., and Howard, B. H.: Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.Mol Cell Biol 2: 1044–1051, 1982PubMedGoogle Scholar
  11. Graham, F. L. and van der Eb, A. J.: A new technique for the assay of infectivity of human adenovirus 5 DNA.Virology 52: 456–467, 1973PubMedGoogle Scholar
  12. Hall, R. E. and Colten, H. R.: Cell-free synthesis of the fourth component of guinea pig complement (C4): identification of a precursor of serum C4 (pro-C4).Proc Natl Acad Sci USA 74: 1707–1710, 1977PubMedGoogle Scholar
  13. Jones, T. R. and Cole, M. D.: Rapid cytoplasmic turnover of c-myc mRNA: requirement of the 3′ untranslated sequences.Mol Cell Biol 7: 4513–4521, 1987PubMedGoogle Scholar
  14. Kioussis, D., Eiferman, F., van de Rijn, P., Gorin, M. B., Ingram, R. S., and Tilgham, S M.: The evolution of α-fetoprotein and albumin. II. The structures of the α-fetoprotein and albumin genes in the mouse.J Biol Chem 256: 1960–1967, 1981Google Scholar
  15. Levi-Strauss, M., Tosi, M., Steinmetz, M., Klein, J., and Meo, T.: Multiple duplications of complement C4 gene correlate with H-2-controlled testosterone-independent expression of its sexlimited isoform, C4-Slp.Proc Natl Acad Sci USA 82: 1746–1750, 1985PubMedGoogle Scholar
  16. Marzluff, W. F. and Huang, R. C. C.: Transcription of RNA in isolated nuclei.In B. D. Hames and S. J. Higgins (eds.):Transcription and Translation. A Practical Approach, pp. 89–129, IRL, Eynsham, Oxford, 1984Google Scholar
  17. Meijlink, F., Curran, T., Miller, A. D., and Verma, I. M.: Removal of a 67-base-pair sequence in the noncoding region of protooncogenefos converts it to a transforming gene.Proc Nod Acad Sci USA 82: 4987–4991, 1985Google Scholar
  18. Messing, J. and Vieira, J.: A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments.Gene 19: 269–276, 1982PubMedGoogle Scholar
  19. Monsma, F. J., Jr, McVittie, L. D., Gerfen, C. R., Mahan, L. C., and Sibley, D. R.: Multiple D2 dopamine receptors produced by alternative RNA splicing.Nature 342: 926–929, 1989PubMedGoogle Scholar
  20. Morris, K. M., Aden, D. P., Knowles, B. B., and Colten, H. R.: Complement biosynthesis by the human hepatoma-derived cell line HepG2.J Clin Invest 70: 906–913, 1982PubMedGoogle Scholar
  21. Nakayama, K., Nonaka, M., Yokoyama, S., Yu, D.-Y., Pattanakitsakul, S.-N., and Takahashi, M.: Recombination of two homologous MHC class III genes of the mouse (C4 and Slp) that accounts for the loss of testosterone dependence of sex-limited protein expression.J Immunol 138: 620–627, 1987PubMedGoogle Scholar
  22. Nonaka, M., Nakayama, K., Yu, D.-Y., Shimizu, A., and Takahashi, M.: Molecular cloning and characterization of complementary and genomic DNA clones for mouse C4 and Slp.Immunol Rev 87: 81–99, 1985aPubMedGoogle Scholar
  23. Nonaka, M., Nakayama, K., Yu, D.-Y., and Takahashi, M.: Complete nucleotide and derived amino acid sequences of the fourth component of mouse complement (C4).J Biol Chem 260: 10936–10943, 1985bPubMedGoogle Scholar
  24. Nonaka, M., Kimura, H., Yu, D. Y., Yokoyama, S., Nakayama, K., and Takahashi, M.: Identification of the 5′-flanking regulatory region responsible for the difference in transcriptional control between mouse complement S4 and Slp genes.Proc Natl Acad Sci USA 83: 7883–7887, 1986PubMedGoogle Scholar
  25. Ogata, R. T. and Sepich, D. S.: Genes for murine fourth complement component (C4) and sex-limited protein (Slp) identified by hybridization to C4- and Slp-specific cDNA.Proc Natl Acad Sci USA 81: 4908–4911, 1984PubMedGoogle Scholar
  26. Parker, K. L., Roos, M. H., and Shreffler, D. C.: Structural characterization of the murine fourth component of complement and sexlimited protein and their precursors: evidence for two loci in the S region of the H-2 complex.Proc Natl Acad Sci USA 76: 5853–5857, 1979PubMedGoogle Scholar
  27. Robins, D. M., Malissen, M., Hood, L., Ferreira, A., Walthall, D., and Mitchell, M.: Multiple C4/Slp genes distinguished by expression after transfection.Mol Cell Biol 6: 134–141, 1986PubMedGoogle Scholar
  28. Rosa, P. A., Sepich, D. S., Robins, D. M., and Ogata, R. T.: Constitutive expression of Slp genes in mouse strain Bl0.WR directed by C4 regulatory sequences.J Immunol 139: 1568–1577, 1987PubMedGoogle Scholar
  29. Sanger, F., Niclen, S., and Coulson, A. R.: DNA sequencing with chain-terminating inhibitors.Proc Natl Acad Sci USA 74: 5463–5467, 1977PubMedGoogle Scholar
  30. Schuler, G. D. and Cole, M. D.: GM-CSF and oncogene mRNA stabilities are independently regulated in trans in a mouse monocytic tumor.Cell 55: 1115–1122, 1988PubMedGoogle Scholar
  31. Sen, R. and Baltimore, D.: Multiple nuclear factors interact with the immunoglobulin enhancer sequences.Cell 46: 705–716, 1986PubMedGoogle Scholar
  32. Sepich, D. S., Noonan, D. J., and Ogata, R. T.: Complete cDNA sequence of the fourth component of murine complement.Proc Natl Acad Sci USA 82: 5895–5899, 1985PubMedGoogle Scholar
  33. Shaw, G. and Kamen, R.: A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation.Cell 46: 659–667, 1986PubMedGoogle Scholar
  34. Shreffler, D. C.: The S region of the mouse major histocompatibility complex (H-2): genetic variation and functional role in the complement system.Transplant Rev 32: 140–167, 1976PubMedGoogle Scholar
  35. Shreffler, D. C.: MHC-linked complement components.In P. Parham and J. Strominger (eds.):Histocompatibility Antigens: Structure and Function, pp. 189–219, Chapman and Hall, London, 1982Google Scholar
  36. Shreffler, D. C. and Owen, R. D.: A serologically detected variant in mouse serum: inheritance and association with the histocompatibility-2 locus.Genetics 48: 9–25, 1963Google Scholar
  37. Sternberg, N., Tiemeier, D., and Enquist, L.: In vitro packaging of a λ dam vector containing EcoRI DNA fragments of Escherichia coli and phage pl.Gene 1: 255–280, 1977PubMedGoogle Scholar
  38. Tosi, M., Levi-Strauss, M., Georgatsou, E., Amor, M., and Meo, T.: Duplications of complement and non-complement genes of the H-2 S region: evolutionary aspects of the C4 isotypes and molecular analysis of their expression variants.Immunol Rev 87: 151–183, 1985PubMedGoogle Scholar
  39. Wilson, T. and Treisman, R.: Removal of poly(A) and consequent degradation of c fos mRNA facilitated by 3′ AU-rich sequences.Nature 336: 396–399, 1988PubMedGoogle Scholar
  40. Yu, D.-Y., Nonaka, M., and Takahashi, M.: Mapping of the transcriptional regulatory domains responsible for the difference in the promoter activity between mouse C4 and Slp (sex-limited protein) genes.J Immunol 141: 4381–4387, 1988PubMedGoogle Scholar
  41. Yu, D.-Y., Huang, Z. M., Murakami, S., Takahashi, M., and Nonaka, M.: Specific binding of a hepatoma nuclear factor to the NF. κB/H2TFl recognition motif found in the C4 promoter, but not in the Slp promoter.J Immunol 143: 2395–2400, 1989PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Kohzo Nakayama
    • 1
  • Sa-nga Pattanakitsakul
    • 1
  • Shigeru Yokoyama
    • 1
  • Masaru Nonaka
    • 1
  • Morinobu Takahashi
    • 1
  • Hiroshi Kimura
    • 2
  1. 1.Department of Immunobiology, Cancer Research InstituteKanazawa UniversityKanazawaJapan
  2. 2.Department of Experimental RadiologyShiga University of Medical ScienceOtsu, ShigaJapan

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