Skip to main content
Log in

Characterizing a human lysyl oxidase chromosomal domain

  • Review
  • Published:
Molecular Biotechnology Aims and scope Submit manuscript

Abstract

The expression of each locus in our genome is regulated by a gene-potentiative mechanism, whereby the gene first assumes the necessary structural conformation to enable transcription. This serves as the cornerstone for the three-tiered regulatory mechanism of potentiation, i.e., the opening of a chromatin domain, initiation of transcription, and transcript elongation. Although this is now generally accepted as the pathway that mediates gene expression, it has never been shown directly to control the expression of any heart-related gene. Lysyl oxidase enzymatically crosslinks members of the extracellular matrix, including elastin and collagen. Formation of these structures is essential to development and tissue repair. This system has enabled us to begin to address the underlying mechanism governing the selection of connective tissue genes for expression. However, before one can dissect this mechanism, it is necessary to define and characterize the locus, i.e., the corresponding genic domain. Our progress toward creating the resources necessary to unravel this mechanism is summarized in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ferns, G. A., Lamb, D. J., and Taylor, A. (1997) The possible role of copper ions in artherogenesis: The Blue Janus. Artherosclerosis 133, 139–152.

    Article  CAS  Google Scholar 

  2. Fornieri, C., Baccarani-Contri, M., Quaglino Jr., D., and Paquali-Rochetti, I. (1987) Lysyl oxidase activity and elastin/glycosaminaoglycan interactions in growing chick and rat aortas. J. Cell Biol. 105, 1463–1469.

    Article  PubMed  CAS  Google Scholar 

  3. Wu, Y., Rich, C. B., Lincecum, J., Trackman, P. C., Kagan, H. M., and Foster, J. A. (1992) Characterization and developmental expression of chick aortic lysyl oxidase. J. Biol. Chem. 267, 24,199–24,206.

    CAS  Google Scholar 

  4. Pinnell, S. R. and Martin, G. R. (1968) The cross-linking of collagen and elastin: Enzymatic conversion of lysine in peptide linkage to α-aminoadipic-δ-semialdehyde (allysine) by an extract from bone. Proc. Natl. Acad. Sci. USA 61, 708–716.

    Article  PubMed  CAS  Google Scholar 

  5. Kagan, H. M. and Trackman, P. C. (1991) Properties and function of lysyl oxidase. Am. J. Respir. Cell. Mol. Biol. 5, 206–210.

    PubMed  CAS  Google Scholar 

  6. Kim, Y., Peyrol, S., So, C.-K., Boyd, C. D., and Csiszar, K. (1999) Coexpression of the lysyl oxidase-like gene (LOXL) and the gene encoding type III procollagen in induced liver fibrosis. J. Cell. Biochem. 72, 181–188.

    Article  PubMed  Google Scholar 

  7. Murawaki, Y., Kusakabe, U., and Hirayama, C. (1991) Serum lysyl oxidase activity in chronic liver disease in comparison with serum levels of proplyl hydroxylase and laminin. Hepatol. 14, 1167–1173.

    Article  CAS  Google Scholar 

  8. Kramsch, D. M., Franzblau, C., and Hollander, W. (1971) The protein and lipid composition of arterial elastin and its relationship to lipid accumulation in the arthersoclerotic plaque. J. Clin. Invest. 50, 1666–1677.

    Article  PubMed  CAS  Google Scholar 

  9. Yu, S. Y. (1971) Cross linking of clastin in human artherosclerotic aortas. I. A preliminary report. Lab. Invest. 25, 121–125.

    PubMed  CAS  Google Scholar 

  10. Medeiros, D. M. and Wildman, R. E. (1997) Newer findings on a unified perspective of copper restriction and cardiomyopathy. Proc. Soc. Exp. Biol. Med. 215, 299–313.

    PubMed  CAS  Google Scholar 

  11. Kuivaniemi, H., Savolainen, E. R., and Kivirikko, K. I. (1984) Human Placental lysyl oxidase: purification, partial characterization, and preparation of two specific antisera to the enzyme. J. Biol. Chem. 259, 6996–7002.

    PubMed  CAS  Google Scholar 

  12. Kagan, H. M., Sullivan, E. R., Olsson III, T. E., and Cronlund, A. L. (1979) Purification and properties of four species of lysyl oxidase from bovine aorta. Biochem. J. 177, 203–214.

    PubMed  CAS  Google Scholar 

  13. Trackman, P. C., Bedell-Hogan, D., Tang, J., and Kagan, H. M. (1992) Post-translational glycosylation and proteolytic processing of a lysyl oxidase precursor. J. Biol. Chem. 267, 8666–8671.

    PubMed  CAS  Google Scholar 

  14. Svinarich, D. M., Twomey, T. A., McCauley, S. P., Krebs, C. J., Yang, T. P., and Krawetz, S. A. (1992) Characterization of the human lysyl oxidase gene locus, J. Biol. Chem. 267, 14,382–14,387.

    CAS  Google Scholar 

  15. Hämäläinen, E.-R., Kemppainen, R., Pihlajaniemi, T., and Kivirikko, K. I. 1993. Structure of the human lysyl oxidase gene. Genomics 17, 544–548.

    Article  PubMed  Google Scholar 

  16. Hämäläinen, E.-R., Jones, T. A., Sheer, D., Taskinen, K., Pihlajaniemi, T., and Kivirikko, K. I. (1991) Molecular cloning of human lysyl oxidase and assignment of the gene to chromosome 5q23.3–31.2. Genomics 11, 508–516.

    Article  PubMed  Google Scholar 

  17. Krebs, C. J. and Krawetz, S. A. (1993) Lysyl oxidase copper-talon complex: a model. Biochem. Biophys. Act. 1202, 7–12.

    CAS  Google Scholar 

  18. Kim, Y., Boyd, C. D., and Csiszar, K. 1995. A new gene with sequence and structural similarity to the gene encoding lysyl oxidase. J. Biol. Chem. 270, 7176–7182.

    Article  PubMed  CAS  Google Scholar 

  19. Kenyon, K., Modi, W. S., Contente, S., and Freidman, R. M. (1993) A novel human cDNA with a predicted protein similar to lysyl oxidase maps to chromosome 15q24–q25. J. Biol. Chem. 268, 18,435–18,437.

    CAS  Google Scholar 

  20. Jourdan-Le Saux C., Le Saux, O., Donlon, T., Boyd, C. D., and Csiszar, K. 1998. The human lysyl oxidase-related gene (LOXL2) maps between markers D8S280 and D8S278 on chromosome 8p21.2–p21.3. Genomics 51, 305–307.

    Article  PubMed  CAS  Google Scholar 

  21. Jourdan-Le Saux, C., Tronecker, H., Bogic, L., Bryant-Greenwood, G. D., Boyd, C. D., and Csiszar, K. (1999) The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues. J. Biol. Chem. 274, 12,939–12,944.

    Article  CAS  Google Scholar 

  22. Saito, H., Papaconstantinou, J., Sato, H., and Goldstein, S. (1997) Regulation of a novel gene encoding a lysyl oxidase-related protein in cellular adhesion and senescence. J. Biol. Chem. 272, 8157–8160.

    Article  PubMed  CAS  Google Scholar 

  23. Kagan, H. M., Williams, M. A., Calaman, S. D., and Berkowitz, E. M. (1983) Histone H1 is a substrate for lysyl oxidase and contains endogenous sodium borotritide-reducible residues. Biochem. Biophys. Res. Commum. 115, 186–192.

    Article  CAS  Google Scholar 

  24. Kagan, H. M., Williams, M. A., Williamson, P. R., and Anderson, J. A. (1984) Influence of sequence and charge on the specificity of lysyl oxidase toward protein and synthetic peptide substrates. J. Biol. Chem. 259, 11,203–11,207.

    CAS  Google Scholar 

  25. Li, W., Nellaiappan, K., Strassmaier, T., Graham, L., Thomas, K. M., and Kagan, H. M. (1997) Localization and activity of lysyl oxidase within nuclei of fibrogenic cells. Proc. Natl. Acad. Sci. USA 94, 12,817–12,822.

    CAS  Google Scholar 

  26. Wakasaki, H. and Ooshima, A. (1990) Immunohistochemical localization of lysyl oxidase with monoclonal antibodies. Lab. Invest. 63, 377–384.

    PubMed  CAS  Google Scholar 

  27. Mello, M. L. S., Contente, S., Vidal, B. C., Planding, W., and Schenck, U. (1995) Modulation of ras transformation affecting chromatin supraorganization as assessed by image analysis. Exp. Cell Res. 220, 374–382.

    Article  PubMed  CAS  Google Scholar 

  28. Sharma, R., Kramer, J. A., and Krawetz, S. A. (1997) Lysyl oxidase, cellular senescence and tumor suppression. Biosci. Rep. 17, 409–414.

    Article  PubMed  CAS  Google Scholar 

  29. Contente, S., Kenyon, K., Rimoldi, D., and Friedman, R. M. (1990) Expression of gene rrg is associated with reversion of NIH 3T3 transformed by LTR-c-H-ras. Science 249, 796–798.

    Article  PubMed  CAS  Google Scholar 

  30. Kenyon, K., Contente, S., Trackman, P. C., Tang, J., Kagan, H. M., and Friedman, R. M. (1991) Lysyl oxidase and rrg messenger RNA. Science 253, 802.

    Article  PubMed  CAS  Google Scholar 

  31. Su, Z.-Z., Yemul, S., Estabrook, A., Friedman, R. M., Zimmer, S. G., and Fisher, P. B. (1995) Transcriptional switching model for the regulation of tumorigenesis and metastasis by the Ha-ras-oncogene: transcriptional changes in the Ha-ras tumor suppressor gene lysyl oxidase. Intl. J. Oncol. 7, 1279–1284.

    CAS  Google Scholar 

  32. Tan, R. S.-P., Taniguchi, T., and Harada, H. (1996) Identification of the lysyl oxidase gene as a target of the antioncogenic transcription factor, IRF-1, and its possible role in tumor suppression. Cancer Res. 56, 2417–2421.

    PubMed  CAS  Google Scholar 

  33. Contente, S., Kenyon, K., Sriraman, P., Subramanyan, S., and Friedman, R. M. (1999) Epigenetic inhibition of lysyl oxidase transcription after transformation by ras oncogene. Mol. Cell. Biochem. 194, 79–91.

    Article  PubMed  CAS  Google Scholar 

  34. Krawetz, S. A., Kramer, J. A., and McCarrey, J. R. (1999) Reprogramming the male gamete genome: a window to successful gene therapy. Gene 234, 1–9.

    Article  PubMed  CAS  Google Scholar 

  35. McCauley, S. P., Schultz, G. S., Bruckner, B. A., Krawetz, S. A., and Yang, T. P. (1996) Effects of transforming growth factor-b1 on extracellular matrix gene expression by human fibroblasts from a laryngeal stenotic lesion. Wound Rep. Reg. 4, 269–277.

    Article  Google Scholar 

  36. Sambrook, J., Fritch, E. F., and Maniatis, T. (1989) A laboratory manual. second edition. Cold Spring Harbor Laboratory Press, USA.

    Google Scholar 

  37. McAlinden, T. E. and Krawetz, S. A. (1994) A practical method to screen libraries of cloned DNA. Anal. Biochem. 218, 237,238.

    Article  PubMed  CAS  Google Scholar 

  38. Nelson, J. E. and Krawetz, S. A. (1995) Mapping the clonally unstable recombinogenic PRM1 → PRM2 → TNP2 region of human 16p13.2. DNA Sequence 5, 163–168.

    PubMed  CAS  Google Scholar 

  39. McAlinden, T. E., Smith, D. I., Smith, S. E., and Krawetz, S. A. (1995) Isolation and characterization of a 1 Mb region of 5q23.3–q31.2 surrounding the human lysyl oxidase gene. J. Mol. Cell Cardiol. 27, 2409–2413.

    Article  PubMed  CAS  Google Scholar 

  40. Chen E. Y., Schlessinger, D., and Kere, J. (1993) Ordered shotgun sequencing, a strategy for integrated mapping and sequencing of YAC clones. Genomics 17, 651–656.

    Article  PubMed  CAS  Google Scholar 

  41. Singh, G. B. and Krawetz, S. A. (1995) CLONE-PLACER: A software tool for simulating contig formation for ordered shotgun sequencing. Genomics 25, 555–558.

    Article  PubMed  CAS  Google Scholar 

  42. Nelson, J. E. and Krawetz, S. A. (1994) Characterization of a human locus in transition. J. Biol. Chem. 269, 31,067–31,073.

    CAS  Google Scholar 

  43. Nelson, J. E. and Krawetz, S. A. (1992) Purification of cloned and genomic DNA by guanidine thiocyanate/isobutyl alcohol fractionation. Anal. Biochem. 207, 197–201.

    Article  PubMed  CAS  Google Scholar 

  44. Nelson, J. E., Khidhir, M., and Krawetz, S. A. (1994) Purification of DNA using guanidine thiocyanate and isobutyl alcohol fractionation in Cell Biology: A Laboratory Handbook. (Celis, J., ed.) Academic Press, Inc., pp. 674–679.

  45. Misener, S. and Krawetz, S. A. (2000) Bioinformatics. Methods and protocols. Humana Press, Totowa, NJ, USA.

    Google Scholar 

  46. Bonfield, J. K., Smith, K. F., and Staden, R. (1995) A new DNA sequence assembly program. Nucleic Acid Res. 24, 4992–4999.

    Article  Google Scholar 

  47. Maxam, A. M. and Gilbert, W. (1977) A new method for sequencing DNA. Proc. Natl. Acad. Sci. USA 74, 560–564.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  49. Dunham I., Shimizu, N., Roe, B. A., Chissoe, S., Hunt, A. R., Collins, J. E., et al. (1999) The DNA sequence of human chromosome 22. Nature 402, 489–495.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephen A. Krawetz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martins, R.P., Krawetz, S.A. Characterizing a human lysyl oxidase chromosomal domain. Mol Biotechnol 15, 225–235 (2000). https://doi.org/10.1385/MB:15:3:225

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/MB:15:3:225

Index Entries

Navigation