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. 1991 May 15;88(10):4309–4312. doi: 10.1073/pnas.88.10.4309

Human X-box-binding protein 1 is required for the transcription of a subset of human class II major histocompatibility genes and forms a heterodimer with c-fos.

S J Ono 1, H C Liou 1, R Davidon 1, J L Strominger 1, L H Glimcher 1
PMCID: PMC51648  PMID: 1903538

Abstract

A complementary DNA encoding a member of the leucine-zipper class of proteins (human X-box-binding protein, hXBP-1) that binds to the 3' end of the conserved X box (X2) of the HLA-DRA major histocompatibility complex gene was recently described. Further gel-retardation analysis has demonstrated that hXBP-1 also binds to HLA-DPB X2 but not to other X2 sequences. Transient transfection of a mammalian expression vector with the hXBP-1 cDNA inserted in the antisense orientation represses the surface expression of HLA-DR and HLA-DP in Raji cells. Cotransfection of the antisense hXBP-1 vector with a HLA-DRA/chloramphenicol acetyltransferase (but not a HLA-DQB/chloramphenicol acetyltransferase) reporter plasmid decreases chloramphenicol acetyltransferase activity in Raji cells and in gamma-interferon-treated HeLa cells relative to cells cotransfected with a control antisense vector. Moreover, hXBP-1 is shown to form a stable heterodimer with the product of the c-fos protooncogene. These data suggest that the hXBP-1 c-fos heterodimer is critical for the transcription of a subset of the human class II major histocompatibility complex genes and that the regulatory mechanisms for the different class II genes are distinct.

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Selected References

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

  1. Basta P. V., Sherman P. A., Ting J. P. Detailed delineation of an interferon-gamma-responsive element important in human HLA-DRA gene expression in a glioblastoma multiform line. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8618–8622. doi: 10.1073/pnas.85.22.8618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benacerraf B. Role of MHC gene products in immune regulation. Science. 1981 Jun 12;212(4500):1229–1238. doi: 10.1126/science.6165083. [DOI] [PubMed] [Google Scholar]
  3. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  4. Boothby M., Liou H. C., Glimcher L. H. Differences in DNA sequence specificity among MHC class II X box binding proteins. J Immunol. 1989 Feb 1;142(3):1005–1014. [PubMed] [Google Scholar]
  5. 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]
  6. Bottazzo G. F., Todd I., Mirakian R., Belfiore A., Pujol-Borrell R. Organ-specific autoimmunity: a 1986 overview. Immunol Rev. 1986 Dec;94:137–169. doi: 10.1111/j.1600-065X.1986.tb01168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Celada A., Maki R. A. DNA binding of the mouse class II major histocompatibility CCAAT factor depends on two components. Mol Cell Biol. 1989 Jul;9(7):3097–3100. doi: 10.1128/mcb.9.7.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cooper M. D., Bucy R. P., George J. F., Lahti J. M., Char D., Chen C. L. T-cell development in birds. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):69–73. doi: 10.1101/sqb.1989.054.01.009. [DOI] [PubMed] [Google Scholar]
  9. Didier D. K., Schiffenbauer J., Woulfe S. L., Zacheis M., Schwartz B. D. Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7322–7326. doi: 10.1073/pnas.85.19.7322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dorn A., Fehling H. J., Koch W., Le Meur M., Gerlinger P., Benoist C., Mathis D. B-cell control region at the 5' end of a major histocompatibility complex class II gene: sequences and factors. Mol Cell Biol. 1988 Oct;8(10):3975–3987. doi: 10.1128/mcb.8.10.3975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Farrell P. J., Rowe D. T., Rooney C. M., Kouzarides T. Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos. EMBO J. 1989 Jan;8(1):127–132. doi: 10.1002/j.1460-2075.1989.tb03356.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Finkel T. H., Cambier J. C., Kubo R. T., Born W. K., Marrack P., Kappler J. W. The thymus has two functionally distinct populations of immature alpha beta + T cells: one population is deleted by ligation of alpha beta TCR. Cell. 1989 Sep 22;58(6):1047–1054. doi: 10.1016/0092-8674(89)90503-5. [DOI] [PubMed] [Google Scholar]
  13. Finn P. W., Kara C. J., Douhan J., 3rd, Van T. T., Folsom V., Glimcher L. H. Interferon gamma regulates binding of two nuclear protein complexes in a macrophage cell line. Proc Natl Acad Sci U S A. 1990 Feb;87(3):914–918. doi: 10.1073/pnas.87.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Ivashkiv L. B., Liou H. C., Kara C. J., Lamph W. W., Verma I. M., Glimcher L. H. mXBP/CRE-BP2 and c-Jun form a complex which binds to the cyclic AMP, but not to the 12-O-tetradecanoylphorbol-13-acetate, response element. Mol Cell Biol. 1990 Apr;10(4):1609–1621. doi: 10.1128/mcb.10.4.1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kappes D., Strominger J. L. Human class II major histocompatibility complex genes and proteins. Annu Rev Biochem. 1988;57:991–1028. doi: 10.1146/annurev.bi.57.070188.005015. [DOI] [PubMed] [Google Scholar]
  17. Kaufman J. F., Auffray C., Korman A. J., Shackelford D. A., Strominger J. The class II molecules of the human and murine major histocompatibility complex. Cell. 1984 Jan;36(1):1–13. doi: 10.1016/0092-8674(84)90068-0. [DOI] [PubMed] [Google Scholar]
  18. Kobr M., Reith W., Herrero-Sanchez C., 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. 1990 Mar;10(3):965–971. doi: 10.1128/mcb.10.3.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Liou H. C., Boothby M. R., Finn P. W., Davidon R., Nabavi N., Zeleznik-Le N. J., Ting J. P., Glimcher L. H. A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter. Science. 1990 Mar 30;247(4950):1581–1584. doi: 10.1126/science.2321018. [DOI] [PubMed] [Google Scholar]
  20. Liou H. C., Boothby M. R., Glimcher L. H. Distinct cloned class II MHC DNA binding proteins recognize the X box transcription element. Science. 1988 Oct 7;242(4875):69–71. doi: 10.1126/science.3140376. [DOI] [PubMed] [Google Scholar]
  21. Luthman H., Magnusson G. High efficiency polyoma DNA transfection of chloroquine treated cells. Nucleic Acids Res. 1983 Mar 11;11(5):1295–1308. doi: 10.1093/nar/11.5.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Matis L. A., Glimcher L. H., Paul W. E., Schwartz R. H. Magnitude of response of histocompatibility-restricted T-cell clones is a function of the product of the concentrations of antigen and Ia molecules. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6019–6023. doi: 10.1073/pnas.80.19.6019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McCutchan J. H., Pagano J. S. Enchancement of the infectivity of simian virus 40 deoxyribonucleic acid with diethylaminoethyl-dextran. J Natl Cancer Inst. 1968 Aug;41(2):351–357. [PubMed] [Google Scholar]
  24. 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]
  25. Miwa K., Strominger J. L. The HLA-DQ beta gene upstream region contains an immunoglobulin-like octamer motif that binds cell-type specific nuclear factors. Nucleic Acids Res. 1987 Oct 12;15(19):8057–8067. doi: 10.1093/nar/15.19.8057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nishimoto H., Kikutani H., Yamamura K., Kishimoto T. Prevention of autoimmune insulitis by expression of I-E molecules in NOD mice. 1987 Jul 30-Aug 5Nature. 328(6129):432–434. doi: 10.1038/328432a0. [DOI] [PubMed] [Google Scholar]
  27. Ono S. J., Bazil V., Levi B. Z., Ozato K., Strominger J. L. Transcription of a subset of human class II major histocompatibility complex genes is regulated by a nucleoprotein complex that contains c-fos or an antigenically related protein. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4304–4308. doi: 10.1073/pnas.88.10.4304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ono S. J., Bazil V., Sugawara M., Strominger J. L. An isotype-specific trans-acting factor is defective in a mutant B cell line that expresses HLA-DQ, but not -DR or -DP. J Exp Med. 1991 Mar 1;173(3):629–637. doi: 10.1084/jem.173.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pujol-Borrell R., Todd I., Doshi M., Bottazzo G. F., Sutton R., Gray D., Adolf G. R., Feldmann M. HLA class II induction in human islet cells by interferon-gamma plus tumour necrosis factor or lymphotoxin. Nature. 1987 Mar 19;326(6110):304–306. doi: 10.1038/326304a0. [DOI] [PubMed] [Google Scholar]
  30. Pullen A. M., Marrack P., Kappler J. W. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. doi: 10.1038/335796a0. [DOI] [PubMed] [Google Scholar]
  31. Reith W., Barras E., Satola S., Kobr M., Reinhart D., Sanchez C. H., Mach B. Cloning of the major histocompatibility complex class II promoter binding protein affected in a hereditary defect in class II gene regulation. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4200–4204. doi: 10.1073/pnas.86.11.4200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Reith W., Satola S., Sanchez C. H., Amaldi I., Lisowska-Grospierre B., Griscelli C., Hadam M. R., 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. 1988 Jun 17;53(6):897–906. doi: 10.1016/s0092-8674(88)90389-3. [DOI] [PubMed] [Google Scholar]
  33. Sakurai M., Strominger J. L. B-cell-specific enhancer activity of conserved upstream elements of the class II major histocompatibility complex DQB gene. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6909–6913. doi: 10.1073/pnas.85.18.6909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sakurai M., Strominger J. L. Studies of expression of the DQ beta promoter and its 5' deletion derivatives in normal and mutant human B cell lines. Tissue Antigens. 1989 Jul;34(1):64–77. doi: 10.1111/j.1399-0039.1989.tb01718.x. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Tsang S. Y., Nakanishi M., Peterlin B. M. B-cell-specific and interferon-gamma-inducible regulation of the HLA-DR alpha gene. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8598–8602. doi: 10.1073/pnas.85.22.8598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. de Préval C., Lisowska-Grospierre B., Loche M., Griscelli C., Mach B. A trans-acting class II regulatory gene unlinked to the MHC controls expression of HLA class II genes. Nature. 1985 Nov 21;318(6043):291–293. doi: 10.1038/318291a0. [DOI] [PubMed] [Google Scholar]

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