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Regulation of human and murine complement: Comparison of 5′ structural and functional elements regulating human and murine complement factor B gene expression

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Abstract

The serine protease complement factor B (Bf), an acute phase plasma protein, is a component of the alternative pathway of complement activation. Previous studies revealed that several cytokines including IFN-γ and IL-1 are involved in mediating acute phase Bf expression. To determine the molecular details of Bf expression we isolated, sequenced and characterized the 5′ flanking regions of the human and murine Bf genes. In both species the Bf transcriptional start site in liver was located <400 by 3′ to the polyadenylation site of the upstream C2 gene. This upstream intergenic region contained >65% nucleotide homology between species. Within this region, an IRS and three heat shock consensus elements were found in the murine sequence in an identical position to that of the human. To examine the functional details of Bf expression, a series of mouse and human Bf promoter - chloramphenicol acetyltransferase (CAT) chimeric gene constructs were transfected into mouse L or human HepG2 cells. Analysis of expression of these fusion gene constructs revealed that 1) cis-acting DNA sequences identified, at least in part, in the 3′ untranslated region of the C2 gene (within the 400 by upstream of the Bf cap site) mediate responsiveness to IL-1 and IFN-γ, 2) the responsiveness to each mediator appears to be conferred by separate upstream regions similar in position and homologous in man and mouse, and 3) the IL-1 responsive region in both species appears to have the characteristics of an enhancer element. The results of this analysis suggest a selective pressure to conserve the intergenic sequence between C2 and Bf genes and that further studies of these sequences will be useful in elucidating mechanisms controlling the acute phase response.

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References

  1. Gitlin JD, Colten HR: Molecular biology of the acute phase plasma proteins. Lymphokines 14: 123–153, 1988

    Google Scholar 

  2. Chaplin DD, Woods DE, Whitehead AS, Goldberger G, Colten HR, Seidman G: Molecular map of the murine S region. Proc. Natl. Acad. Sci. USA 80: 6947–6951, 1983

    Google Scholar 

  3. Carroll MC, Campbell RD, Bentley DR, Porter RR: A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature 307: 237–241, 1984

    Google Scholar 

  4. Perlmutter DH, Colten HR, Grossberger D, Strominger J, Seidman G, Chaplin DD: Expression of complement protein C2 and factor B in transfected L cells. J. Clin. Invest. 76: 1449–1454, 1985

    Google Scholar 

  5. Ramadori G, Sipe JD, Dinarello CA, Mizel SB, Colten HR: Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin-1 (IL-1) and purified human IL-1. J. Exp. Med. 162: 930–942, 1985

    Google Scholar 

  6. Perlmutter DH, Dinarello CA, Punsal PI, Colten HR: Cachectin/tumor necrosis factor regulates hepatic acute phase gene expression. J. Clin. Invest. 78: 1349–1354, 1986

    Google Scholar 

  7. Perlmutter DH, Goldberger G, Dinarello CA, Mizel SB, Colten HR: Regulation of class III major histocompatibility complex gene products by interleukin-1. Science 232: 850–852, 1986

    Google Scholar 

  8. Strunk RC, Cole FS, Perlmutter DH, Colten HR: γ-interferon increases expression of class III complement genes C2 and factor B in human monocytes and in murine fibroblasts transfected with human C2 and factor B genes. J. Biol. Chem. 260: 15280–15285, 1985

    Google Scholar 

  9. Wu L, Morley BJ, Campbell RD: Cell-specific expression of human complement protein factor B gene: Evidence for the role of two distinct 5′-flanking elements. Cell 48: 331–342, 1987

    Article  CAS  PubMed  Google Scholar 

  10. Woods DE, Markham AF, Ricker AT, Goldberger G, Colten HR: Isolation of cDNA clones for the human complement protein factor B, a class III major histocompatibility complex gene product. Proc. Natl. Acad. Sci. USA 79: 5661–5665, 1982

    Google Scholar 

  11. Sanger F, Nicklen S, Coulson AR: DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA 74: 5463–5467, 1977

    Google Scholar 

  12. Enquist LW, Vandewoude GF, Wagner M, Smiley JR, Summers WC: Gene 7: 335–342, 1979

    Google Scholar 

  13. Gorman CM, Moffat LF, Howard BH: Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cell. Mol. Cell. Biol. 2: 1044–1051, 1982

    Google Scholar 

  14. Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18: 5294–5299, 1979

    CAS  PubMed  Google Scholar 

  15. Walker MD, Edlund T, Boulet AM, Rutter WJ: Cell-specific expression controlled by the 5′-flanking region of insulin and chymotrypsin genes. Nature 306: 557–561, 1983

    Google Scholar 

  16. Morley BJ, Campbell RD: Internal homologies of the Ba fragment from human complement component factor B, a class III MHC antigen. EMBO J. 3: 153–157, 1984

    Google Scholar 

  17. Laimins LA, Khoury G, Gorman CM, Howard BH, Gross P: Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc. Natl. Acad. Sci. USA 79: 6453–6457, 1982

    Google Scholar 

  18. Katz Y, Cole FS, Strunk RC: Synergism between γ-interferon and lipopolysaccharide for synthesis of factor B, but not C2, in human fibroblast. J. Exp. Med. 167: 1–14, 1988

    Google Scholar 

  19. Ramadori G, Sipe JD, Colten HR: Expression and regulation of the murine serum amyloid A (SAA) gene in extrahepatic sites. J. Immunol. 135: 3645–3647, 1985

    Google Scholar 

  20. Lee SH, Starkey PM, Gordon S: Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80. J. Exp. Med. 161: 475–489, 1985

    Google Scholar 

  21. Friedman RL, Stark GR: Alpha-interferon-ιnduced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature 314: 637–639, 1985

    Google Scholar 

  22. Israel A, Kimura A, Fournier A, Fellous M, Kourilsky P: Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene. Nature 322: 743–746, 1986

    Google Scholar 

  23. Besta PV, Sherman PA, Ting JP-Y: Identification of an interferon-γ response region 5′ of the human histocompatibility leukocyte antigen DRα chain gene which is active in human glioblastoma multiforme lines. J. Immunol. 138: 1275–1280, 1987

    Google Scholar 

  24. Dorn A, Durand B, Matting C, LeMeur M, Benoist C, Mathis D: Conserved major histocompatibility complex class II boxes — X and Y — are transcriptional control elements and specifically bind nuclear proteins. Proc. Natl. Acad. Sci. USA 84: 6209–6253, 1987

    Google Scholar 

  25. Benech P, Vigneron M, Paretz D, Revel M, Chebath J: Interferon-responsive regulatory elements in the promoter of the human 2′, 5′-oligo(A) synthetase gene. Mol. Cell. Biol. 7: 4498–4504, 1987

    Google Scholar 

  26. Blanar MA, Boettger EC, Flavell RA: Transcriptional activation of HLA-DR alpha by interferon gamma requires a transacting protein. Proc. Natl. Acad. Sci. USA 85: 4672–4676, 1988

    Google Scholar 

  27. Karin M, Haslinger A, Heguy A, Deitlin T, Cooke T: The metal responsive elements act as positive modulators of human metallothionein-IIA enhancer activity. Mol. Cell. Biol. 7: 606–613, 1987

    Google Scholar 

  28. Fujita T, Ohno S, Yasumitsu H, Taniguchi T: Delimitation and properties of DNA sequences required for the regulated expression of human interferon-β gene. Cell 41: 489–496, 1985

    Google Scholar 

  29. Chandler VL, Maler BA, Yamamoto KR: DNA sequences bound specifically by glucocorticoid receptor in vitro render heterologous promoter hormone responsive in vivo. Cell 33: 489–499, 1983

    Google Scholar 

  30. Angel P, Baumann I, Stein B, Delins H, Rahmsdorf HJ, Herrlich P: 12–0-tetradecanoyl-phorbol-13-acetate (TPA) induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′-flanking region. Mol. Cell. Biol. 7: 2256–2266, 1987

    Google Scholar 

  31. Pelham HRB, Bienz M: A synthetic heat-shock promoter element confers heat-inducibility on the herpes simplex virus thymidine kinase gene. EMBO J. 1: 1473–1477, 1982

    Google Scholar 

  32. Kozak M: Point mutations define a sequence flanking the AVG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44: 283–292, 1986

    Article  CAS  PubMed  Google Scholar 

  33. Gross-Bellard M, Oudd P, Chambon P: Isolation of high-molecular weight DNA from mammalian cells. Eur. J. Biochem. 36: 32–38, 1973

    Google Scholar 

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Authors and Affiliations

  1. The Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, Children's Hospital, 400 South Kingshighway Blvd., 63110, St. Louis, MO, USA

    Masaru Nonaka, Jonathan D. Gitlin & Harvey R. Colten

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  1. Masaru Nonaka
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  2. Jonathan D. Gitlin
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  3. Harvey R. Colten
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Nonaka, M., Gitlin, J.D. & Colten, H.R. Regulation of human and murine complement: Comparison of 5′ structural and functional elements regulating human and murine complement factor B gene expression. Mol Cell Biochem 89, 1–14 (1989). https://doi.org/10.1007/BF00228274

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  • DOI: https://doi.org/10.1007/BF00228274

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