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Structure and expression of the three MHC-linked HSP70 genes

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Abstract

A duplicated locus encoding the major heat shock-induced protein HSP70 is located in the major histocompatibility complex (MHC) class III region 92 kilobases (kb) telomeric to the C2 gene. Nucleotide sequence analysis of the two intronless genes, HSP70-1 and HSP70-2, has shown that they encode an identical protein product of 641 amino acids. A third intronless gene, HSP70-Hom, has also been identified 4 kb telomeric to the HSP70-1 gene. This encodes a more basic protein of 641 amino acids which has 90% sequence similarity with HSP70-1. In order to investigate the expression of the three (MHC)-linked HSP70 genes individually by northern blot analysis, we have isolated locus-specific probes from the 3′ untranslated regions of the genes. The HSP70-1 and HSP70-2 genes have been shown to be expressed at high levels as a ∼ 2.4 kb mRNA in cells heat-shocked at 42°C. HSP70-1 is also expressed constitutively at very low levels. The HSP70-Hom gene, which has no heat shock consensus sequence in its 5′ flanking sequence, is expressed as a ∼3 kb mRNA at low levels both constitutively and following heat shock.

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References

  • Amin, J., Ananthan, J., and Voellmy, R.: Key features of heat shock regulatory elements. Mol Cell Biol 8: 3761–3769, 1988

    Google Scholar 

  • Batchelor, J. R. and McMichael, A. J.: Progress in understanding HLA and disease associations. Br Med Bull 43: 156–183, 1987

    Google Scholar 

  • Cameron, P. U., Tabarias, H. A., Pulendran, B., Robinson, W., and Dawkins, R. L.: Conservation of the central MHC genome: PFGE mapping and RFLP analysis of complement, HSP70, and TNF genes in the goat. Immunogenetics 31: 253–264, 1990

    Google Scholar 

  • Chappel, T. G., Welch, W. J., Schlossman, D. M., Palter, K. B., Schlesinger, M. J., and Rothman, J. E.: Uncoating ATPase is a member of the 70 kilodalton family of stress proteins. Cell 45: 3–13, 1986

    Google Scholar 

  • Chiang, H. L., Terlecky, S. R., Plant, C. P., and Dice, J. F.: A role for a 70 kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246: 382–385, 1989

    Google Scholar 

  • Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J., and Rutter, W. J.: Isolation of biologically active RNA from sources enriched in ribonuclease. Biochemistry 18: 5294–5299, 1979

    CAS  PubMed  Google Scholar 

  • Dworniczak, B. and Mirault, M.: Structure and expression of a human gene coding for a 71 kD heat shock ‘cognate’ protein. Nucleic Acids Res 15: 5181–5197, 1987

    Google Scholar 

  • Feinberg, A. P. and Vogelstein, B.: A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. (Addendum.) Anal Biochem 137: 266–267, 1984

    CAS  PubMed  Google Scholar 

  • Fourney, R. M., Miyokoshi, J., Day, R. F., and Paterson, M. C.: Northern blotting: efficient RNA staining and transfer. Focus 10: 5–7, 1988

    Google Scholar 

  • Goate, A. M., Cooper, D. N., Hall, C., Leung, T. K. C., Solomon, E., and Lim, L.: Localisation of a human heat-shock HSP70 gene sequence to chromosome 6 and detection of two other loci by somatic-cell hybrid and restriction fragment length polymorphism analysis. Hum Genet 75: 123–128, 1987

    Google Scholar 

  • Harrison, G. S., Drabkin, H. A., Kao, F. T., Hartz, J., Hart, I. M., Chu, E. H. Y., Wu, B. J., and Morimoto, R. I.: Chromosomal location of the human genes encoding major heat-shock protein HSP70. Somatic Cell Mol Genet 13: 119–130, 1987

    Google Scholar 

  • Hunt, C. and Morimoto, R. I.: Conserved features of eukaryotic HSP70 genes revealed by comparison with the nucleotide sequence of human HSP70. Proc Natl Acad Sci USA 82: 6455–6459, 1985

    CAS  PubMed  Google Scholar 

  • Lamb, J. R., Bal, V., Mendez-Samperio, P., Mehlert, A., So, A., Rothbard, J., Jindal, S., Young, R. A., and Young, D. B.: Stress proteins may provide a link between the immune response to infection and autoimmunity: Int Immunol 1: 191–196, 1989

    Google Scholar 

  • Leung, T. K. C., Rajendran, M. Y., Monfries, C., Hall, C., and Lim, L.: The human heat-shock protein family. Biochem J 267: 125–132, 1990

    Google Scholar 

  • Levi-Strauss, M., Carroll, M. C., Steinmetz, M., and Meo, T.: A previously undetected MHC gene with an unusual periodic structure. Science 240: 201–204, 1988

    Google Scholar 

  • Lindquist, S.: The heat-shock response. Annu Rev Biochem 55: 1151–1191, 1986

    Article  CAS  PubMed  Google Scholar 

  • Lindquist, S. and Craig, E. A.: The heat-shock proteins. Annu Rev Genet 22: 631–677, 1988

    Article  CAS  PubMed  Google Scholar 

  • Maniatis, T., Fritsch, E. F., and Sambrook, L.: Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1982

    Google Scholar 

  • Morel, Y., Bristow, J., Gitelman, S. E., and Miller, W. L.: Transcript encoded on the opposite strand of the human steroid 21-hydroxylase/complement component C4 gene locus. Proc Natl Acad Sci USA 86: 6582–6586, 1989

    Google Scholar 

  • Morgan, W. D., Williams, G. T., Morimoto, R. I., Greene, J., Kingston, R. E., and Tjian, R.: Two transcriptional activators, CCAAT-box-binding transcription factor and heat shock transcription factor, interact with a human HSP70 gene promoter. Mol Cell Biol 7: 1129–1138, 1987

    Google Scholar 

  • Res, P. C. M., Schaar, C. G., Breedveld, F. C., van Eden, W., van Embden, J. D. A., Cohen, I. R., and de Vries, R. R. P.: Synovial fluid T cell reactivity against the 65 kD heat-shock protein of mycobacteria in early onset of chronic arthritis. Lancet 2: 478–480, 1988

    Google Scholar 

  • Sargent, C. A., Dunham, I., and Campbell, R. D.: Identification of multiple HTF-island associated genes in the human major histocompatibility complex class III region. EMBO J 8: 2305–2312, 1989a

    Google Scholar 

  • Sargent, C. A., Dunham, I., Trowsdale, J., and Campbell, R. D.: Human major histocompatibility complex contains genes for the major heat shock protein HSP70. Proc Natl Acad Sci USA 84: 1968–1972, 1989b

    Google Scholar 

  • Southern, E. M.: Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 503–517, 1975

    CAS  PubMed  Google Scholar 

  • Spies, T., Breshahan, M., and Strominger, J. L.: Human major histocompatibility complex contains a minimum of 19 genes between the complement cluster and HLA-B. Proc Natl Acad Sci USA 86: 8955–8958, 1989

    Google Scholar 

  • Taylor, I. C. A. and Kingston, R. E.: Factor substitution in a human HSP70 gene promotor: TATA-dependent and TATA-independent interactions. Mol Cell Biol 10: 165–175, 1990

    Google Scholar 

  • Ting, J. and Lee, S. A.: Human gene encoding the 78,000-Dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation. DNA 7: 275–286, 1988

    CAS  PubMed  Google Scholar 

  • Todd, J. A., Acha-Orbea, H., Bell, J. I., Chao, N., Fronek, Z., Jacob, C. O., McDermott, M., Sinha, A. A., Timmerman, L., Steinman, L. and McDevitt, H. O.: A molecular basis for MHC class II-associated autoimmunity. Science 240: 1003–1009, 1988

    Google Scholar 

  • van Eden, W., Thole, J. E. R., van der Zee, R., Noordzij, A., van Embden, J. D. A., Hensen, E. J., and Cohen, I. R.: Cloning of the mycobacterial epitope recognised by T lymphocytes in adjuvant arthritis. Nature 331: 171–173, 1988

    Google Scholar 

  • Watowich, S. S. and Morimoto, R. I.: Complex regulation of heat-shock-and glucose-responsive genes in human cells. Mol Cell Biol 8: 393–405, 1988

    Google Scholar 

  • Williams, G. T., McCanahan, T. K., and Morimoto, R. I.: Ela transactivation of the human HSP70 promotor is mediated through the basal transcription complex. Mol Cell Biol 9: 2574–2587, 1989

    CAS  PubMed  Google Scholar 

  • Wu, B. J. and Morimoto, R. I.: Transcription of the human HSP70 gene is induced by serum stimulation. Proc Natl Acad Sci USA 82: 6070–6074, 1985

    Google Scholar 

  • Wu, B. J., Hunt, C., and Morimoto, R. I.: Structure and expression of the human gene encoding major heat shock protein HSP70. Mol Cell Biol 5: 330–341, 1985

    Google Scholar 

  • Wu, B. J., Kingston, R. E., and Morimoto, R. I.: Human HSP70 promoter contains at least two distinct regulatory domains. Proc Natl Acad Sci USA 83: 629–633, 1986

    Google Scholar 

  • Wurst, W., Benesch, C., Drabent, B., Rothermel, E., Benecke, B.-J., and Günther, E.: Localisation of heat shock protein 70 genes inside the rat major histocompatibility complex close to class III genes. Immunogenetics 30: 46–49, 1989

    Google Scholar 

  • Yasuhiro, D. and Kishimoto, S.: Elevated expression of heat-shock protein gene in the fibroblasts of patients with scleroderma. Clin Sci 78: 419–422, 1990

    Google Scholar 

  • Young, R. A.: Stress proteins and immunology. Annu Rev Immunol 8: 401–420, 1990

    Google Scholar 

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The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers M34267-9.

Address correspondence and offprint requests to: R. D. Campbell.

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Milner, C.M., Duncan Campbell, R. Structure and expression of the three MHC-linked HSP70 genes. Immunogenetics 32, 242–251 (1990). https://doi.org/10.1007/BF00187095

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  • DOI: https://doi.org/10.1007/BF00187095

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