Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Dec;87(23):9226–9230. doi: 10.1073/pnas.87.23.9226

Interferon gamma response region in the promoter of the human DPA gene.

Z Yang 1, M Sugawara 1, P D Ponath 1, L Wessendorf 1, J Banerji 1, Y Li 1, J L Strominger 1
PMCID: PMC55137  PMID: 2123552

Abstract

The interferon gamma (IFN-gamma) response region of the human class II major histocompatibility complex gene, DPA, has been localized to a 52-base-pair (bp) DNA fragment in the proximal promotor at -107 to -55 bp after transfection into HeLa cells of a series of 5', 3', and gap deletion mutants linked to a reporter gene, human growth hormone, as well as of synthetic oligonucleotides fused to the heterologous promoter thymidine kinase. The 52-mer sequence contains the X and Y box elements conserved in all class II genes; their presence is indispensable for IFN-gamma inducibility. Furthermore, an additional 5 bp immediately 5' of the X box of the DPA gene are necessary and sufficient for IFN-gamma induction. This region may contain an IFN-gamma response element. A closely related sequence has also been found in the vicinity of the critical deletion sites of three other well-studied class II gene promoters, all of which require a much longer sequence 5' of the X box. A fourth element, the W element, located about 15 bp 5' of the X box in all class II genes, is clearly of little importance in IFN-gamma inducibility of the DPA gene.

Full text

PDF
9226

Images in this article

9227Image
on p.9227
9227Image
on p.9227
9228Image
on p.9228
9228Image
on p.9228
9229Image
on p.9229

Selected References

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

  1. Amaldi I., Reith W., Berte C., Mach B. Induction of HLA class II genes by IFN-gamma is transcriptional and requires a trans-acting protein. J Immunol. 1989 Feb 1;142(3):999–1004. [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Benoist C., Mathis D. Regulation of major histocompatibility complex class-II genes: X, Y and other letters of the alphabet. Annu Rev Immunol. 1990;8:681–715. doi: 10.1146/annurev.iy.08.040190.003341. [DOI] [PubMed] [Google Scholar]
  5. Blanar M. A., Baldwin A. S., Jr, Flavell R. A., Sharp P. A. A gamma-interferon-induced factor that binds the interferon response sequence of the MHC class I gene, H-2Kb. EMBO J. 1989 Apr;8(4):1139–1144. doi: 10.1002/j.1460-2075.1989.tb03484.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blanar M. A., Boettger E. C., Flavell R. A. Transcriptional activation of HLA-DR alpha by interferon gamma requires a trans-acting protein. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4672–4676. doi: 10.1073/pnas.85.13.4672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blanck G., Strominger J. L. Cosmid clones in the HLA-DZ and -DP subregions. Hum Immunol. 1990 Mar;27(3):265–268. doi: 10.1016/0198-8859(90)90056-u. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. 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]
  11. Dedrick R. L., Jones P. P. Sequence elements required for activity of a murine major histocompatibility complex class II promoter bind common and cell-type-specific nuclear factors. Mol Cell Biol. 1990 Feb;10(2):593–604. doi: 10.1128/mcb.10.2.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dianzani F., Zucca M., Scupham A., Georgiades J. A. Immune and virus-induced interferons may activate cells by different derepressional mechanisms. Nature. 1980 Jan 24;283(5745):400–402. doi: 10.1038/283400a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Enoch T., Zinn K., Maniatis T. Activation of the human beta-interferon gene requires an interferon-inducible factor. Mol Cell Biol. 1986 Mar;6(3):801–810. doi: 10.1128/mcb.6.3.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fan C. M., Maniatis T. Two different virus-inducible elements are required for human beta-interferon gene regulation. EMBO J. 1989 Jan;8(1):101–110. doi: 10.1002/j.1460-2075.1989.tb03353.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goodbourn S., Zinn K., Maniatis T. Human beta-interferon gene expression is regulated by an inducible enhancer element. Cell. 1985 Jun;41(2):509–520. doi: 10.1016/s0092-8674(85)80024-6. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Israel A., Kimura A., Fournier A., Fellous M., Kourilsky P. Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene. Nature. 1986 Aug 21;322(6081):743–746. doi: 10.1038/322743a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. Krieg P. A., Melton D. A. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. doi: 10.1016/0076-6879(87)55027-3. [DOI] [PubMed] [Google Scholar]
  24. McKnight S. L., Kingsbury R. Transcriptional control signals of a eukaryotic protein-coding gene. Science. 1982 Jul 23;217(4557):316–324. doi: 10.1126/science.6283634. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Okada K., Prentice H. L., Boss J. M., Levy D. J., Kappes D., Spies T., Raghupathy R., Mengler R. A., Auffray C., Strominger J. L. SB subregion of the human major histocompatibility complex: gene organization, allelic polymorphism and expression in transformed cells. EMBO J. 1985 Mar;4(3):739–748. doi: 10.1002/j.1460-2075.1985.tb03691.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Paul W. E., Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. doi: 10.1146/annurev.iy.05.040187.002241. [DOI] [PubMed] [Google Scholar]
  29. Reid L. E., Brasnett A. H., Gilbert C. S., Porter A. C., Gewert D. R., Stark G. R., Kerr I. M. A single DNA response element can confer inducibility by both alpha- and gamma-interferons. Proc Natl Acad Sci U S A. 1989 Feb;86(3):840–844. doi: 10.1073/pnas.86.3.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Rutherford M. N., Hannigan G. E., Williams B. R. Interferon-induced binding of nuclear factors to promoter elements of the 2-5A synthetase gene. EMBO J. 1988 Mar;7(3):751–759. doi: 10.1002/j.1460-2075.1988.tb02872.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Schamboeck A., Korman A. J., Kamb A., Strominger J. L. Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain. Nucleic Acids Res. 1983 Dec 20;11(24):8663–8675. doi: 10.1093/nar/11.24.8663. [DOI] [PMC free article] [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. Servenius B., Rask L., Peterson P. A. Class II genes of the human major histocompatibility complex. The DO beta gene is a divergent member of the class II beta gene family. J Biol Chem. 1987 Jun 25;262(18):8759–8766. [PubMed] [Google Scholar]
  36. Sherman P. A., Basta P. V., Moore T. L., Brown A. M., Ting J. P. Class II box consensus sequences in the HLA-DR alpha gene: transcriptional function and interaction with nuclear proteins. Mol Cell Biol. 1989 Jan;9(1):50–56. doi: 10.1128/mcb.9.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sloan J. H., Boss J. M. Conserved upstream sequences of human class II major histocompatibility genes enhance expression of class II genes in wild-type but not mutant B-cell lines. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8186–8190. doi: 10.1073/pnas.85.21.8186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Thanos D., Mavrothalassitis G., Papamatheakis J. Multiple regulatory regions on the 5' side of the mouse E alpha gene. Proc Natl Acad Sci U S A. 1988 May;85(9):3075–3079. doi: 10.1073/pnas.85.9.3075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Tsang S. Y., Nakanishi M., Peterlin B. M. Mutational analysis of the DRA promoter: cis-acting sequences and trans-acting factors. Mol Cell Biol. 1990 Feb;10(2):711–719. doi: 10.1128/mcb.10.2.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Widera G., Burkly L. C., Pinkert C. A., Böttger E. C., Cowing C., Palmiter R. D., Brinster R. L., Flavell R. A. Transgenic mice selectively lacking MHC class II (I-E) antigen expression on B cells: an in vivo approach to investigate Ia gene function. Cell. 1987 Oct 23;51(2):175–187. doi: 10.1016/0092-8674(87)90145-0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES