Abstract
Regulation of HLA class II transcription is complex, with both locus-specific and allele-specific polymorphisms associated with consensus regulatory region promoter elements. In order to evaluate the potential function of allele-specific elements, HLA-DQB1 transcripts and in vivo footprinting of the DQB1 promoter were studied in human cell lines inducible for HLA class II expression. In the heterozygous melanoma cell line Me9229/18, differential expression was observed for two DQB1 alleles. This variation was reflected in both steady-state and inducible transcripts, although methylation patterns of the promoter elements were similar for both alleles. This in vivo allelic difference expression, which correlates with previous studies of in vitro reporter gene transcription, indicates the potential for functionally important differences in tissue-specific and inducible expression attributable to promoter region polymorphism in HLA genes.
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Andersen, L. C., Beaty, J. S., Nettles, J. W., Seyfried, C. E., Nepom, G. T., and Nepom, B. S. Allelic polymorphism in transcriptional regulatory regions of HLA-DQB genes. J Exp Med 173: 181–192, 1991
Anichini, A., Castelli, C., Sozzi, G., Fossati, G., and Parmiani, G. Differential susceptibility to recombinant interferon-gamma-induced HLA-DQ antigen modulation among clones from a human metastatic melanoma. J Immunol 140: 183–191, 1988
Benichou, B. and Strominger, J. L. Class II-antigen-negative patient and mutant B-cell lines represent at least three, and probably four, distinct genetic defects defined by complementation analysis. Proc Natl Acad Sci USA 88: 4285–4288, 1991
Calman, A. F. and Peterlin, B. M. Mutant human B cell lines deficient in class II major histocompatibility complex transcription. J Immunol 139: 2489–2495, 1987
Dostani, N., Thierry, F., and Yaniv, M. A dimer of BPV-IE2 containing a protease resistant core interacts with its DNA target. EMBO J 7: 3807–3816, 1988
Gaur, L., Shewey, L., Sharkey-Mathis, D., and Nepom, G. T. Transcriptional regulatory elements in primate MHC-DQB genes. Transgenics 1: 267–276, 1994
Glimcher, L. H. and Kara, C. J. Sequences and factors: a guide to MHC class II transcription. Annu Rev Immunol 10: 13–49, 1992
Hasegawa, S. L. and Boss, J. M. Two B cell factors bind the HLA-DRA X box region and recognize different subsets of Mhc class II promoters. Nucleic Acids Res 19: 6269–6276, 1991
Hume, C. R. and Lee, J. S. Congenital immunodeficiencies associated with absence of HLA class II antigens on lymphocytes result from distinct mutations in trans-acting factors. Hum Immunol 26: 288–309, 1989
Hume, C. R. and Lee, J. S. Functional analysis of Cis-linked regulatory sequences in the HLA-DRA promoter by transcription in vitro. Tissue Antigens 36: 108–115, 1990
Kara, C. J. and Glimcher, L. H. Three in vivo promoter phenotypes in MHC class II deficient combined immunodeficiency. Immunogenetics 37: 227–230, 1993
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
Liou, H.-C., Boothby, M. R., Finn, P. W., Davidon, R., Nabavi, N., Zeleznik-Le, N. J., Ting, J. P., and Glimcher, L. H. A new member of the leucine zipper class of proteins that binds to the HLA DR α promoter. Science 247: 1581–1584, 1990
Louis, P., Vincent, R., Cavadore, P., Clot, J., and Eliaou, J.-F. Differential transcriptional activities of HLA-DR genes in the various haplotypes. J Immunol 153: 5059–5067, 1994
Maxam, A. M. and Gilbert, W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol 65: 499–560, 1980
Morzycka-Wroblewska, E., Harwood, J. I., Smith, J. R., and Kagnoff, M. F. Structure and evolution of the promoter regions of the DQA genes. Immunogenetics 37: 364–372, 1993
Mueller, P. R. and Wold, A. In vivo footprinting of a muscle specific enhancer by ligation mediated PCR. Science 246: 780–786, 1989
Nakajima-Iijima, S., Hamada, H., Reddy, P., and Kakynaga, T. Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci USA 82: 6133–6137, 1985
Nomura, N., Ota, M., Tsuji, K., and Inoko, H. HLA-DQB1 genotyping by a modified PCR-RFLP method combined with group-specific primers. Tissue Antigens 38: 53–59, 1991
Reichstetter, S., Krellner, P. H., Meenzen, C. M., Kalden, J. R., and Wassmuth, R. Comparative analysis of sequence variability in the upstream regulatory region of the HLA-DQB1 gene. Immunogenetics 39: 207–212, 1994
Reith, W., Satola, S., Sanchez, c. H., Amaldi, I., Lisowska-Grospierre, B., Griscelli, C., Hadam, M. R., and Mach, B. Congential immunodeficiency with a regulatory defecti in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X. Cell 53: 897–906, 1988
Reith, W., Siegrist, c.-A, Durand,., Barras, E., and Mach, B. Function of major histocompatibility complex class II promoters requires cooperative binding between factors RFX and NF-Y. Proc Natl Acad Sci USA 91: 554–558, 1994
Rigaud, g.l, Paiola, F., and Accolla, R. S. In vivo modification of major histocompatibility complex class II DRA promoter occupancy mediated by the AIR-1 trans-activator. Eur J Immnol 24; 2415–2420, 1994
Seidi, C., Saraiya, C., Osterweil, Z., Fu, Y. P., and Lee, J. S. Genetic complexity of retulatory mutants defective for HLA class II gene expression. J Immunol 148: 1576–1584, 1992
Sherman, P. A., Basta, P. V., and Ting, J. P. Upstream DNA sequences required for tissue-specific expression of the HLA-DRα gene. Proc Natl Acad Sci USA 84: 4254–4258, 1987
Sherman, P. A., Basta, P. V., Moore, T. L., Brown, A. M. and Ting, J. P.-Y. Class II box consensus sequences in the HLA-DRα gene: transcriptional function and interaction with nuclear proteins. Mol Cell Biol 9: 50–56, 1989
Siebert, P. D. and Larrick, J. W. PCR mimics: competitive DNA fragments for use as internal standards in quantitative PCR. Bio Techniques 14: 244–249, 1993
Sukiennicki, T. L., Shewey, L. M., and Nepom, G. T. Locus and allele-specific DNA-protein in the HLA-DQB1 X-box. Immunol Res 12: 317–329, 1993
Tsang, S. Y., Nakanishi, M., and Peterlin, B. M. Mutational analysis of the DRA promoter: cis-acting sequences and trans-acting factors. Mol Cell Biol 10: 711–719, 1990
Turco, e., Manfras, B. J., Ge, L., Rudert, W. A., and Trucco, M. The X boxes from promoters of HLA class II B genes at different loci do not compete for nuclear protein-specific binding. Immunogenetics 32: 117–128, 1990
Vilen, B. J., Penta, J. F., and Ting, J. T.-Y. Structural constraints within a trimeric transcriptional regulatory region: constitutive and interferon-gamma inducible expression of the HLA-DRA gene. J Biol Chem 267: 23728–23734, 1992
Woolfrey, A., West, K., and Nepom, G. T. DNA-protein interactions in the upstream regulatory region of the HLA-DQ class II gene promoter. Allergy Immunol 1, in press
Wright, K. L. and Ting, J. P.-Y. In vivo footprint analysis of the HLA-DRA gene promoter: cell-specific interaction at the octamer site and up-regulation of X box binding by interferon gamma. Proc Natl Acad Sci USA 89: 7601–7605, 1992
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Nepon, G.T., Chung, J. & West, K.A. Differential expression of HLA-DQB1 alleles in a heterozygous cell line. Immunogenetics 42, 143–148 (1995). https://doi.org/10.1007/BF00178589
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DOI: https://doi.org/10.1007/BF00178589