Abstract
Studies on the regulation of a major histocompatibility complex (MHC) class II gene,HLA-DQA1, in Ia-positive cells (Raji, a human B-lymphoma cell line) and in isogenic la-negative cells (RJ2.2.5, a mutant of Raji altered at theAIR-1 locus) are reported. As previously found,AIR-1 is required in its entirety for the activity of an enhancer factor, the absence of which abolishes transcription of MHC class II genes. In this paper, we show thatHLA-DQA1 gene expression can be directed by an enhancerless promoter. The fact that this promoter is inactive in the RJ2.2.5 mutant suggests that thetrans-acting element determined by theAIR-1 locus is not only an enhancer factor as previously described, but also acts at the MHC class II promoter level.
Similar content being viewed by others
References
Accolla, R. S.: Human B cell variants immunoselected against a single la antigen subset have lost expression of several Ia antigen subsets.J Exp Med 157: 1053–1058, 1983
Accolla, R. S., Carra, G., and Guardiola, J.: Reactivation by a transacting factor of human major histocompatibility complex Ia gene expression in interspecies hybrids between an Ia-negative human B-cell variant and an Ia-positive mouse B-cell lymphoma.Proc Natl Acad Sci USA 82: 5145–5149, 1985a
Accolla, R. S., Scarpellino, L., Carra, G., and Guardiola, J.: Transacting element(s) operating across species barriers positively regulate expression of major histocompatibility complex class II genes.J Exp Med 162: 1116–1133, 1985b
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
Auffray, C., Lillie, J. W., Korman, A. J., Boss, J. M., Fréchin, N., Guillemot, F., Cooper, J., Mulligan, R. C., and Strominger, J. L.: Structure and expression of HLA-DQα and -DXα genes: interallelic alternate splicing of the HLA-DQα gene and functional splicing of the HLA-DXα gene using a retroviral vector.Immunogenetics 26: 63–73, 1987
Del Pozzo, G. and Guardiola, J.: Mummy DNA identified.Nature 339: 431–432, 1989
DePrèval, C., Lisowska-Grospierre, L., Loche, M., Griscelli, C., and Mach, B.: A trans-acting class II regulatory gene unlinked to the MHC controls expression of HLA class II genes.Nature 318: 291–293, 1985
Dorn, A., Durand, B., Marfing, C., Lemeur, M., Benoist, C., and Mathis, D.: Conserved MHC 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
Dorn, A., Fehling, J. H., Koch, W., Lemeur, M., Gerlinger, P., Benoist, C., and Mathis, D.: B-cell control region at the 5′ end of a MHC class II gene: sequences and factors.Mol Cell Biol 8: 3975–3987, 1988
Gillies, S. D., Folsom, V., and Tonegawa, S.: Cell type-specific enhancer element associated with mouse MHC gene, Eß.Nature 310: 594–597, 1984
Gladstone, P. and Pious, D.: Identification of a trans-acting function regulating HLA-DR expression in DR-negative B cell variants.Som Cell Genet 6: 285–298, 1980
Guardiola, J. and Iaccarino, M.: Escherichia coli altered in the transport of branched chain amino acids.J Bacteriol 108: 1034–1046, 1971
Guardiola, J., Scarpellino, L., Carra, G., and Accolla, R. S.: Stable integration of mouse DNA into la-negative human B-lymphoma cells causes re-expression of the human la-positive phenotype.Proc Natl Acad Sci USA 83: 7415–7418, 1986
Klein, G., Giovanella, B., Westmann, A., Stehlin, J. S., and Mumford, D.: An EBV genome negative cell line established from an American Burkitt lymphoma: receptor characteristics, EBV infectibility and permanent conversion into EBV-positive; studies by infection.Intervirology 5: 319–334, 1975
Koch, N., Benoist, C., and Mathis, D.: Anatomy of a new B-cell specific enhancer.Mol Cell Biol 9: 303–311, 1988a
Koch, N., Candeias, S., Guardiola, J., Accolla, R. S., Benoist, C., and Mathis, D.: An enhancer factor defect in a mutant Burkitt lymphoma cell line.J Exp Med 167: 1781–1790, 1988b
Korman, A. J., Boss, J. M., Spies, T., Sorrentino, R., Okada, K., and Strominger, J. L.: Genetic complexity and expression of human class II histocompatibility antigens.Immunol Rev 84: 175–215, 1985
Long, E. O., Mach, B., and Accolla, R. S.: Ia-negative B-cell variants reveal a coordinate regulation in the transcription of the HLA class II gene family.Immunogenetics 19: 349–352, 1984
Luckow, B. and Schütz, G.: CAT construction with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements.Nucleic Acids Res 15: 5490, 1987
Maffei, A., Perfetto, C., Ombra, N., Del Pozzo, G., and Guardiola, J.: Transcriptional and post-transcriptional regulation of human MHC class II genes requires the synthesis of short-lived proteins.J Immunol 142: 1357–1365, 1989
Miwa, K., Doyle, C., and Strominger, J. L.: Sequence-specific interactions of nuclear factors with conserved sequences of human class II MHC genes.Proc Natl Acad Sci USA 84: 4939–4943, 1987
Okada, K., Boss, J. M., Prentice, H., Spies, T., Mengler, R., Auffray, C., Lillie, J., Grossberger, D., and Strominger, J. L.: Gene organization of the DC and DX subregions of the human major histocompatibility complex.Proc Natl Acad Sci USA 82: 3410–3414, 1985
Reith, N., Satola, S., Sanchez Herrero, C., Amaldi, I., LisowskaGrospierre, L., Griscelli, C., Hadam, M. R., and Mach, B.: Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X.Cell 53: 897–906, 1988
Sherman, P. A., Basta, P. V., and Ting, J. P. Y.: Upstream DNA sequences required for tissue-specific expression of the HLA-DR alpha gene.Proc Natl Acad Sci USA 84: 4254–4258, 1987
Sloan, J. H. and Boss, J. M.: Conserved upstream sequences of human class II major histocompatibility genes enhance expression of class II genes in wild-type but not B-cell lines.Proc Natl Acad Sci USA 85: 8186–8190, 1988
Stimac, E., Lyons, S., and Pious, D.: Transcription of HLA class II genes in the absence of B-cell-specific octamer binding factor.Mol Cell Biol 8: 3734–3739, 1988
Sullivan, K. E. and Peterlin, B. M.: Transcriptional enhancers in the HLA-DQ subregion.Mol Cell Biol 7: 3315–3319, 1987
Sullivan, K. E., Calman, A. F., Nakanishi, M., Tsang, S. Y., Wang, Y., and Peterlin, B. M.: A model for the transcriptional regulation of MHC class II genes.Immunol Today 8: 289–293, 1987
Wang, Y., Larsen, A. S., and Peterlin, B. M.: A tissue-specific transcriptional enhancer is found in the body of the HLA-DR alpha gene.J Exp Med 166: 625–636, 1987
Wirth, T. and Baltimore, D.: Nuclear factor NF-κB can interact functionally with its cognate binding site to provide lymphoid-specific promoter function.EMBO J 7: 3109–3113, 1989
Yang, Z., Accolla, R. S., Pious, D., Zegers, B. J. M., 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
Author information
Authors and Affiliations
Additional information
The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M33765.
Rights and permissions
About this article
Cite this article
Ombra, M.N., Del Pozzo, G., Perfetto, C. et al. Effect of theAIR-1 locus on the activation of an enhancerlessHLA-DQA1 promoter. Immunogenetics 31, 368–376 (1990). https://doi.org/10.1007/BF02115012
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02115012