Skip to main content
Log in

An HLA-DRα promoter DNA-binding protein is expressed ubiquitously and maps to human chromosomes 22 and 5

  • Original Articles
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The class II major histocompatibility complex antigens are a family of integral membrane proteins whose expression is tissue-specific and developmentally regulated. Three consensus sequences, X1, X2, and Y, separated by an interspace element, is found upstream from all class II genes. Deletion of each of these sequences eliminates expression of class II genes in vitro or in transgenic mice. Here we further characterize the expression of a cDNA encoding a DNA binding protein (human X-box binding protein, hXBP-1) which, like the proteins in whole nuclear extract, recognizes both the X2 promoter element of the human DR α and DP β and mouse A α genes. The hXBP-1 cDNA hybridizes to human RNA species of approximately 2.2 kilobases (kb) and 1.6 kb, which are expressed in class II negative as well as class II positive cells. hXBP-1 transcripts are present in several class II deficient mutant B cell lines, although in one such line, 6.1.6, levels were somewhat reduced. Chromosome mapping studies demonstrate that hXBP-1 arises from a small gene family, two of whose members map to human chromosomes 5 and 22. Taken together, these data suggest a high degree of complexity in the transcriptional control of the class II gene family.

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

  • Accolla, R. S., Jotterand-Bellomo, M., Scarpellino, L., Maffei, A., Carra, G., and Guardiola, J.: aIr-1, a newly found locus on mouse chromosome 16 encoding a trans-acting activator factor for MHC class II gene expression. J Exp Med 164: 369–374, 1986

    Google Scholar 

  • Boetgger, E., Blanar, M., and Flavell, R.: Cycloheximide, an inhibitor of protein synthesis, prevents λ interferon-induced expression of class II mRNA in a macrophage cell line. Immunogenetics 28: 215–220, 1988

    Google Scholar 

  • Boothby, M., Liou, H.-C., and Glimcher, L. H.: Differences in DNA sequence specificity among MHC class II X box binding proteins. J Immunol 142: 1995–1014, 1989

    Google Scholar 

  • Calman, A. F. and Peterlin, B. M.: Evidence for a trans-acting factor that regulates the transcription of class II MHC genes: Genetic and functional analysis. Proc Natl Acad Sci USA 85: 8830–8834, 1988

    Google Scholar 

  • Chavrier, P., Lemaire, P., Revelant, O., Bravo, R., and Charnay, P.: Characterization of a mouse multigene family that encodes zinc finger structure. Mol Cell Biol 8: 1319–1326, 1988

    Google Scholar 

  • 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, 1979

    CAS  PubMed  Google Scholar 

  • Dorn, A., Durand, B., Marfing, C., LeMeur, M., Benoist, C., and 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: 6249–6253, 1987

    Google Scholar 

  • Dorn, A., Benoist, C., and Mathis, D.: New B-lymphocyte-specific enhancer-binding protein. Mol Cell Biol 9: 312–320, 1989

    Google Scholar 

  • Evans, R. M. and Hollenberg, S. M.: Zinc fingers: Gilt by association. Cell 52: 1–3, 1988

    Google Scholar 

  • Finn, P. W., Van, T. T., Accolla, R. S., and Glimcher, L. H.: Loss of a DNA-protein complex correlates with extinguished major histocompatibility complex class II expression in a human B cell. J Exp Med 171: 2159–2164, 1990

    Google Scholar 

  • Gladstone, P. and Pious, D.: Identification of a trans-acting function regulating HLA-DR expression in a DR-negative B cell variant. Somat Cell Mol Genet 6: 285–298, 1980

    Google Scholar 

  • Gonzalez, G. A., Yamamoto, K. K., Fischer, W. H., Karr, D., Menzel, P., Biggs, W., Vale, W. W., and Montminy, M. R.: A cluster of phosphorylation sites on the cyclic-AMP-regulated nuclear factor CREB predicted by its sequence. Nature 337: 749–752, 1989

    Google Scholar 

  • Graves, B. J., Johnson, P. F., and McKnight, S. L.: Homologous recognition of a promoter domain common to the MSV LTR and the HSV tk gene. Cell 44: 565–576, 1986

    Google Scholar 

  • Hoeffler, J. P., Meyer, T. E., Yun, Y., Jameson, J. L., and Habener, J. F.: Cyclic-AMP-responsive DNA-binding protein: Structure based on a cloned placental cDNA. Science 242: 1430–1433, 1988

    Google Scholar 

  • Hoey, T. and Levine, M.: Divergent homeo box protein recognize similar DNA sequences in Drosophila. Nature 332: 858–861, 1988

    Google Scholar 

  • Ivashkiv, L. B., Liou, H.-C., Kara, C. J., Lamph, W. W., Verma, I. M., and Glimcher, L. H.: mXBP and c-Jun form a complex which binds to the cyclic-AMP but not to the TPA response element. Mol Cell Biol 10: 1609–1621, 1990

    Google Scholar 

  • Jones, K. A., Kadonaga, J. T., Rosenfeld, P. J., Kelly, T. J., and Tijian, R.: A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell 48: 79–89, 1987

    Google Scholar 

  • Kara, C. J., Liou, H.-C., Ivashkiv, L. B., and Glimcher, L. H.: A cDNA for a human CRE-binding protein which is distinct from CREB and expressed preferentially in brain. Mol Cell Biol 10: 1347–1357, 1990

    Google Scholar 

  • Kobr, M., Reith, W., Herrero-Sanchez, C., and Mach, B.: Two DNA-binding proteins discriminate between the promoters of different members of the major histocompatibility complex class II multigene family. Mol Cell Biol 10: 965–971, 1990

    Google Scholar 

  • Koch, W., Candeias, S., Guardiola, J., Accolla, R., Benoist, C., Mathis, D.: An enhancer factor defect in a mutant Burkitt lymphoma cell line. J Exp Med 167: 1781–1790, 1988

    Google Scholar 

  • Landschulz, W. H., Johnson, P. F., and McKnight, S. L.: The leucine zipper: A hypothetical structure common to a new class of DNA binding proteins. Nature 240: 1759–1764, 1988

    Google Scholar 

  • Lee, J. S.: Regulation of HLA class II gene expression. In B. Dupont (ed.) Immunobiology of HLA, pp. 49–62, Springer, New York, 1988

    Google Scholar 

  • Liou, H.-C., Boothby, M. R., and Glimcher, L. H.: Distinct cloned class II MHC DNA binding proteins recognize the X box transcription element. Science 242: 69–71, 1988

    Google Scholar 

  • Liou, H.-C., Boothby, M. R., Finn, P. W., Davidon, R., Nabavi, N., Zeleznik-Le, N. J., Ting, J. P.-Y., and Glimcher, L. H.: A new member of the leucine zipper class of proteins binds to the HLA DRα promoter. Science 247: 1581–1584, 1990a

    Google Scholar 

  • Liou, H.-C., Ivashkiv, L. B., Kara, C. J., and Glimcher, L. H.: Transcriptional regulation of MHC class II gene expression: Are MHC class II genes coordinately regulated? In I. K. Egorov and C. S. David (eds.): Transgenic Mice and Research in MHC Mutants, pp. 133–142, Springer, New York, 1990b

    Google Scholar 

  • Lisowska-Grospierre, B., Charron, D. J., de Preval, C., Durandy, A., Griscelli, C., and Mach, B.: A defect in the regulation of major histocompatibility complex class II gene expression in human HLA-DR negative lymphocytes from patients with combined immunodeficiency syndrome. J Clin Invest 76: 2385, 1985

    Google Scholar 

  • Mannhalter, J. W., Wolf, H., De Cunha, M., Gadner, H., and Eibl, M.: Induction of an alloresponse by lymphocytes from a patient with MHC class II deficiency. FASEB J (Abstract) 3: A1274, 1989

    Google Scholar 

  • Miwa, K., Doyle, C., and Strominger, J. L.: Sequence-specific interaction of nuclear factors with conserved sequences of human class II major histocompatibility complex genes. Proc Natl Acad Sci USA 84: 4939–4943, 1987

    Google Scholar 

  • Ono, S. J., Liou, H.-C., Strominger, J. L., and Glimcher, L. H.: Transient expression of antisense hXBP-1 RNA inhibits the transcription of a subset of human class II major histocompatibility complex genes. Proc Natl Acad Sci USA 88: 4304–4308, 1991

    Google Scholar 

  • Reith, W., Satola, S., Herrero-Sanchez, C., Amaldi, I., Lisowska-Grospierre, B., Griscelli, C., Hadam, M. R., and Mach, B.: Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DRα promoter binding protein, RF-X. Cell 53: 897–906, 1988

    Google Scholar 

  • Reith, W., Herrero-Sanchez, C., Kobr, M., Silacci, P., Berte, C., Barras, E., Fey, S., and Mach, B.: MHC regulatory factor RFX has a novel DNA-binding domain and a functionally independent dimerization domain. Genes Dev 4: 1528–1540, 1990

    Google Scholar 

  • Sen, R. and Baltimore, D.: Inducibility of κ-immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism. Cell 47: 921–928, 1986

    Google Scholar 

  • Sherman, P. A., Basta, P. V., and Ting, J. P.-Y.: Upstream DNA sequences required for tissue-specific expression of the HLA-DRα gene. Proc Natl Acad Sci USA 84: 4254–4258, 1987

    Google Scholar 

  • Shows, T. B.: In M. C. Rattazzi, J. G. Scandalios, G. S. Whitt (eds.), Isozymes: Current Topics in Biological and Medical Research vol 10, pp. 323–339, A. T. Liss, New York, 1983

    Google Scholar 

  • Shows, T. B., Brown, J. A., Haley, L. L., Byers, M. G., Eddy, R. L., Cooper, E. S., and Goggin, A. P.: Assignment of the β-glucuronidase structural gene to the pter-q22 region of chromosome 7 in man. Cytogenet Cell Genet 21: 99–104, 1978

    Google Scholar 

  • Shows, T. B., Sakaguchi, A. Y., and Naylor, S. L.: In H. Harris and K. Hirshchhorn (eds.): Advances in Human Genetics vol 12, pp. 341–352, Plenum Press, New York, 1982

    Google Scholar 

  • Shows, T., Eddy, R., Haley, L., Byers, M., Henry, M., Fujita, T., Matsui, H., and Taniguchi, T.: Interleukin-2 (IL-2) is assigned to human chromosome 4. Somat Cell Mol Gen 10: 315–318, 1984

    Google Scholar 

  • Sloan, J. H. and Boss, J. M.: Conserved upstream sequences of human class II MHC genes enhance expression of class II genes in wildtype but not mutant B-cell lines. Proc Natl Acad Sci USA 85: 8186–8190, 1988

    Google Scholar 

  • Yang, Z., Accolla, R., Pious, D., Zegers, B., and Strominger, J. L.: Two distinct genetic loci regulating class II gene expression are defective in human mutant and patient cell lines. EMBO J 7: 1965–1972, 1988

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liou, HC., Eddy, R., Shows, T. et al. An HLA-DRα promoter DNA-binding protein is expressed ubiquitously and maps to human chromosomes 22 and 5. Immunogenetics 34, 286–292 (1991). https://doi.org/10.1007/BF00211992

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00211992

Keywords

Navigation