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. 1988 Sep;85(18):6909–6913. doi: 10.1073/pnas.85.18.6909

B-cell-specific enhancer activity of conserved upstream elements of the class II major histocompatibility complex DQB gene.

M Sakurai 1, J L Strominger 1
PMCID: PMC282088  PMID: 3137578

Abstract

A 95-base-pair immediate upstream sequence of the human class II major histocompatibility complex DQB gene containing the conserved X and Y elements showed enhancer activity in a transient expression assay. An "enhancer test plasmid" harboring the bacterial chloramphenicol acetyltransferase gene under the control of a truncated simian virus 40 enhancerless early promoter was employed. The DQB sequence inserted into this plasmid was active as an enhancer in Raji cells (human Burkitt lymphoma cells) but not active in Jurkat cells (human T-cell leukemia cells) or in HeLa cells (human cervical carcinoma cells). This cell-type specificity suggests that this enhancer activity may be involved in the tissue specificity of the DQB gene that is normally expressed only in mature B cells, macrophages, and thymic epithelial cells. Deletion analysis showed that both X and Y box sequences are essential for the full activity of the enhancer sequence and that these two sequences may function in a cooperative manner as cis-acting elements. Further deletions were used to define the 5' border of the X element. These results suggest that previously characterized protein factors that bind to X and Y include transcription factors involved in the cell-type specificity of this enhancer activity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Accolla R. S., Carra G., Guardiola J. Reactivation by a trans-acting 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 U S A. 1985 Aug;82(15):5145–5149. doi: 10.1073/pnas.82.15.5145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Accolla R. S. Human B cell variants immunoselected against a single Ia antigen subset have lost expression of several Ia antigen subsets. J Exp Med. 1983 Mar 1;157(3):1053–1058. doi: 10.1084/jem.157.3.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  4. Bienz M., Pelham H. R. Heat shock regulatory elements function as an inducible enhancer in the Xenopus hsp70 gene and when linked to a heterologous promoter. Cell. 1986 Jun 6;45(5):753–760. doi: 10.1016/0092-8674(86)90789-0. [DOI] [PubMed] [Google Scholar]
  5. Boss J. M., Strominger J. L. Cloning and sequence analysis of the human major histocompatibility complex gene DC-3 beta. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5199–5203. doi: 10.1073/pnas.81.16.5199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boss J. M., Strominger J. L. Regulation of a transfected human class II major histocompatibility complex gene in human fibroblasts. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9139–9143. doi: 10.1073/pnas.83.23.9139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Calman A. F., Peterlin B. M. Mutant human B cell lines deficient in class II major histocompatibility complex transcription. J Immunol. 1987 Oct 1;139(7):2489–2495. [PubMed] [Google Scholar]
  8. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Collins T., Korman A. J., Wake C. T., Boss J. M., Kappes D. J., Fiers W., Ault K. A., Gimbrone M. A., Jr, Strominger J. L., Pober J. S. Immune interferon activates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4917–4921. doi: 10.1073/pnas.81.15.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dorn A., Bollekens J., Staub A., Benoist C., Mathis D. A multiplicity of CCAAT box-binding proteins. Cell. 1987 Sep 11;50(6):863–872. doi: 10.1016/0092-8674(87)90513-7. [DOI] [PubMed] [Google Scholar]
  11. Dorn A., Durand B., Marfing C., Le Meur M., Benoist C., 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 U S A. 1987 Sep;84(17):6249–6253. doi: 10.1073/pnas.84.17.6249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gillies S. D., Folsom V., Tonegawa S. Cell type-specific enhancer element associated with a mouse MHC gene, E beta. Nature. 1984 Aug 16;310(5978):594–597. doi: 10.1038/310594a0. [DOI] [PubMed] [Google Scholar]
  13. Gillies S. D., Morrison S. L., Oi V. T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. doi: 10.1016/0092-8674(83)90014-4. [DOI] [PubMed] [Google Scholar]
  14. Gladstone, Pious D. Stable variants affecting B cell alloantigens in human lymphoid cells. Nature. 1978 Feb 2;271(5644):459–461. doi: 10.1038/271459a0. [DOI] [PubMed] [Google Scholar]
  15. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Graves B. J., Johnson P. F., McKnight S. L. Homologous recognition of a promoter domain common to the MSV LTR and the HSV tk gene. Cell. 1986 Feb 28;44(4):565–576. doi: 10.1016/0092-8674(86)90266-7. [DOI] [PubMed] [Google Scholar]
  18. Israël A., Kimura A., Kieran M., Yano O., Kanellopoulos J., Le Bail O., Kourilsky P. A common positive trans-acting factor binds to enhancer sequences in the promoters of mouse H-2 and beta 2-microglobulin genes. Proc Natl Acad Sci U S A. 1987 May;84(9):2653–2657. doi: 10.1073/pnas.84.9.2653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  20. Kelly A., Trowsdale J. Complete nucleotide sequence of a functional HLA-DP beta gene and the region between the DP beta 1 and DP alpha 1 genes: comparison of the 5' ends of HLA class II genes. Nucleic Acids Res. 1985 Mar 11;13(5):1607–1621. doi: 10.1093/nar/13.5.1607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kimura A., Israël A., Le Bail O., Kourilsky P. Detailed analysis of the mouse H-2Kb promoter: enhancer-like sequences and their role in the regulation of class I gene expression. Cell. 1986 Jan 31;44(2):261–272. doi: 10.1016/0092-8674(86)90760-9. [DOI] [PubMed] [Google Scholar]
  22. Klein G., Giovanella B., Westman A., Stehlin J. S., Mumford D. An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection. Intervirology. 1975;5(6):319–334. doi: 10.1159/000149930. [DOI] [PubMed] [Google Scholar]
  23. Koeffler H. P., Ranyard J., Yelton L., Billing R., Bohman R. Gamma-interferon induces expression of the HLA-D antigens on normal and leukemic human myeloid cells. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4080–4084. doi: 10.1073/pnas.81.13.4080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Korman A. J., Boss J. M., Spies T., Sorrentino R., Okada K., Strominger J. L. Genetic complexity and expression of human class II histocompatibility antigens. Immunol Rev. 1985 Jul;85:45–86. doi: 10.1111/j.1600-065x.1985.tb01130.x. [DOI] [PubMed] [Google Scholar]
  25. Malissen B., Price M. P., Goverman J. M., McMillan M., White J., Kappler J., Marrack P., Pierres A., Pierres M., Hood L. Gene transfer of H-2 class II genes: antigen presentation by mouse fibroblast and hamster B-cell lines. Cell. 1984 Feb;36(2):319–327. doi: 10.1016/0092-8674(84)90225-3. [DOI] [PubMed] [Google Scholar]
  26. Miwa K., Doyle C., Strominger J. L. Sequence-specific interactions of nuclear factors with conserved sequences of human class II major histocompatibility complex genes. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4939–4943. doi: 10.1073/pnas.84.14.4939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Noelle R. J., Kuziel W. A., Maliszewski C. R., McAdams E., Vitetta E. S., Tucker P. W. Regulation of the expression of multiple class II genes in murine B cells by B cell stimulatory factor-1 (BSF-1). J Immunol. 1986 Sep 1;137(5):1718–1723. [PubMed] [Google Scholar]
  28. O'Sullivan D. M., Larhammar D., Wilson M. C., Peterson P. A., Quaranta V. Structure of the human Ia-associated invariant (gamma)-chain gene: identification of 5' sequences shared with major histocompatibility complex class II genes. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4484–4488. doi: 10.1073/pnas.83.12.4484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Okada K., Boss J. M., Prentice H., Spies T., Mengler R., Auffray C., Lillie J., Grossberger D., Strominger J. L. Gene organization of DC and DX subregions of the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1985 May;82(10):3410–3414. doi: 10.1073/pnas.82.10.3410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pober J. S., Collins T., Gimbrone M. A., Jr, Cotran R. S., Gitlin J. D., Fiers W., Clayberger C., Krensky A. M., Burakoff S. J., Reiss C. S. Lymphocytes recognize human vascular endothelial and dermal fibroblast Ia antigens induced by recombinant immune interferon. Nature. 1983 Oct 20;305(5936):726–729. doi: 10.1038/305726a0. [DOI] [PubMed] [Google Scholar]
  31. Queen C., Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell. 1983 Jul;33(3):741–748. doi: 10.1016/0092-8674(83)90016-8. [DOI] [PubMed] [Google Scholar]
  32. Rabourdin-Combe C., Mach B. Expression of HLA-DR antigens at the surface of mouse L cells co-transfected with cloned human genes. Nature. 1983 Jun 23;303(5919):670–674. doi: 10.1038/303670a0. [DOI] [PubMed] [Google Scholar]
  33. Salter R. D., Alexander J., Levine F., Pious D., Cresswell P. Evidence for two trans-acting genes regulating HLA class II antigen expression. J Immunol. 1985 Dec;135(6):4235–4238. [PubMed] [Google Scholar]
  34. Selden R. F., Howie K. B., Rowe M. E., Goodman H. M., Moore D. D. Human growth hormone as a reporter gene in regulation studies employing transient gene expression. Mol Cell Biol. 1986 Sep;6(9):3173–3179. doi: 10.1128/mcb.6.9.3173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Serfling E., Lübbe A., Dorsch-Häsler K., Schaffner W. Metal-dependent SV40 viruses containing inducible enhancers from the upstream region of metallothionein genes. EMBO J. 1985 Dec 30;4(13B):3851–3859. doi: 10.1002/j.1460-2075.1985.tb04157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sherman P. A., Basta P. V., Ting J. P. Upstream DNA sequences required for tissue-specific expression of the HLA-DR alpha gene. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4254–4258. doi: 10.1073/pnas.84.12.4254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Snyder D. S., Beller D. I., Unanue E. R. Prostaglandins modulate macrophage Ia expression. Nature. 1982 Sep 9;299(5879):163–165. doi: 10.1038/299163a0. [DOI] [PubMed] [Google Scholar]
  38. Sullivan K. E., Peterlin B. M. Transcriptional enhancers in the HLA-DQ subregion. Mol Cell Biol. 1987 Sep;7(9):3315–3319. doi: 10.1128/mcb.7.9.3315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yang Z., Accolla R. S., Pious D., Zegers B. J., Strominger J. L. Two distinct genetic loci regulating class II gene expression are defective in human mutant and patient cell lines. EMBO J. 1988 Jul;7(7):1965–1972. doi: 10.1002/j.1460-2075.1988.tb03034.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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