Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1989 Jul;8(7):2009–2014. doi: 10.1002/j.1460-2075.1989.tb03608.x

Interactions of alpha- and gamma-interferon in the transcriptional regulation of the gene encoding a guanylate-binding protein.

T Decker 1, D J Lew 1, Y S Cheng 1, D E Levy 1, J E Darnell Jr 1
PMCID: PMC401078  PMID: 2507314

Abstract

Transcriptional regulation of the gene encoding a guanylate-binding protein (GBP) by the two interferon (IFN) types was studied. GBP gene transcription was regulated by alpha IFN in a manner identical to that of previously described IFN-stimulated genes (ISGs): rapid induction, without a need for protein synthesis, followed by a protein synthesis-dependent suppression of transcription to basal levels within 6 h. Transcriptional induction by gamma IFN was equally rapid and independent of ongoing protein synthesis but remained at elevated levels for greater than 24 h. Experiments employing combined treatments with IFNs of both types revealed that induction of the GBP gene by gamma IFN overrides the alpha IFN-induced active repression and reverses the alpha IFN-induced repressed state. Moreover, the alpha IFN-mediated repression of ISG54, a gene normally responsive to only alpha IFN, is also reversed by gamma IFN. Induction of GBP by gamma IFN is presumably mediated by a factor different from the recently described activator Interferon Stimulated Gene Factor 3 (ISGF3) because induction of this factor was not observed upon treatment of cells with gamma IFN. Finally, a complex set of reinforcing or synergistic effects were observed when induction of the GBP gene was evoked by a combined treatment with the two IFN types.

Full text

PDF
2012

Images in this article

2009Image
on p.2009
2010Image
on p.2010
2011Image
on p.2011
2011Image
on p.2011
2011Image
on p.2011
2012Image
on p.2012

Selected References

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

  1. Aguet M., Dembić Z., Merlin G. Molecular cloning and expression of the human interferon-gamma receptor. Cell. 1988 Oct 21;55(2):273–280. doi: 10.1016/0092-8674(88)90050-5. [DOI] [PubMed] [Google Scholar]
  2. Caplen H. S., Gupta S. L. Differential regulation of a cellular gene by human interferon-gamma and interferon-alpha. J Biol Chem. 1988 Jan 5;263(1):332–339. [PubMed] [Google Scholar]
  3. Cheng Y. S., Becker-Manley M. F., Chow T. P., Horan D. C. Affinity purification of an interferon-induced human guanylate-binding protein and its characterization. J Biol Chem. 1985 Dec 15;260(29):15834–15839. [PubMed] [Google Scholar]
  4. Cheng Y. S., Becker-Manley M. F., Nguyen T. D., DeGrado W. F., Jonak G. J. Nonidentical induction of the guanylate binding protein and the 56K protein by type I and type II interferons. J Interferon Res. 1986 Aug;6(4):417–427. doi: 10.1089/jir.1986.6.417. [DOI] [PubMed] [Google Scholar]
  5. Cheng Y. S., Colonno R. J., Yin F. H. Interferon induction of fibroblast proteins with guanylate binding activity. J Biol Chem. 1983 Jun 25;258(12):7746–7750. [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  8. Costa R. H., Lai E., Grayson D. R., Darnell J. E., Jr The cell-specific enhancer of the mouse transthyretin (prealbumin) gene binds a common factor at one site and a liver-specific factor(s) at two other sites. Mol Cell Biol. 1988 Jan;8(1):81–90. doi: 10.1128/mcb.8.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Czarniecki C. W., Fennie C. W., Powers D. B., Estell D. A. Synergistic antiviral and antiproliferative activities of Escherichia coli-derived human alpha, beta, and gamma interferons. J Virol. 1984 Feb;49(2):490–496. doi: 10.1128/jvi.49.2.490-496.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
  14. Gray P. W., Goeddel D. V. Structure of the human immune interferon gene. Nature. 1982 Aug 26;298(5877):859–863. doi: 10.1038/298859a0. [DOI] [PubMed] [Google Scholar]
  15. Gray P. W., Leung D. W., Pennica D., Yelverton E., Najarian R., Simonsen C. C., Derynck R., Sherwood P. J., Wallace D. M., Berger S. L. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503–508. doi: 10.1038/295503a0. [DOI] [PubMed] [Google Scholar]
  16. Grayson D. R., Costa R. H., Xanthopoulos K. G., Darnell J. E., Jr A cell-specific enhancer of the mouse alpha 1-antitrypsin gene has multiple functional regions and corresponding protein-binding sites. Mol Cell Biol. 1988 Mar;8(3):1055–1066. doi: 10.1128/mcb.8.3.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hofer E., Darnell J. E., Jr The primary transcription unit of the mouse beta-major globin gene. Cell. 1981 Feb;23(2):585–593. doi: 10.1016/0092-8674(81)90154-9. [DOI] [PubMed] [Google Scholar]
  18. Kelly J. M., Gilbert C. S., Stark G. R., Kerr I. M. Differential regulation of interferon-induced mRNAs and c-myc mRNA by alpha- and gamma-interferons. Eur J Biochem. 1985 Dec 2;153(2):367–371. doi: 10.1111/j.1432-1033.1985.tb09312.x. [DOI] [PubMed] [Google Scholar]
  19. Kessler D. S., Levy D. E., Darnell J. E., Jr Two interferon-induced nuclear factors bind a single promoter element in interferon-stimulated genes. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8521–8525. doi: 10.1073/pnas.85.22.8521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kessler D. S., Pine R., Pfeffer L. M., Levy D. E., Darnell J. E., Jr Cells resistant to interferon are defective in activation of a promoter-binding factor. EMBO J. 1988 Dec 1;7(12):3779–3783. doi: 10.1002/j.1460-2075.1988.tb03262.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Larner A. C., Chaudhuri A., Darnell J. E., Jr Transcriptional induction by interferon. New protein(s) determine the extent and length of the induction. J Biol Chem. 1986 Jan 5;261(1):453–459. [PubMed] [Google Scholar]
  22. Larner A. C., Jonak G., Cheng Y. S., Korant B., Knight E., Darnell J. E., Jr Transcriptional induction of two genes in human cells by beta interferon. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6733–6737. doi: 10.1073/pnas.81.21.6733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lengyel P. Biochemistry of interferons and their actions. Annu Rev Biochem. 1982;51:251–282. doi: 10.1146/annurev.bi.51.070182.001343. [DOI] [PubMed] [Google Scholar]
  24. Levy D. E., Kessler D. S., Pine R., Reich N., Darnell J. E., Jr Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control. Genes Dev. 1988 Apr;2(4):383–393. doi: 10.1101/gad.2.4.383. [DOI] [PubMed] [Google Scholar]
  25. Levy D., Larner A., Chaudhuri A., Babiss L. E., Darnell J. E., Jr Interferon-stimulated transcription: isolation of an inducible gene and identification of its regulatory region. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8929–8933. doi: 10.1073/pnas.83.23.8929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Luster A. D., Unkeless J. C., Ravetch J. V. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985 Jun 20;315(6021):672–676. doi: 10.1038/315672a0. [DOI] [PubMed] [Google Scholar]
  27. Luster A. D., Weinshank R. L., Feinman R., Ravetch J. V. Molecular and biochemical characterization of a novel gamma-interferon-inducible protein. J Biol Chem. 1988 Aug 25;263(24):12036–12043. [PubMed] [Google Scholar]
  28. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Newburger P. E., Ezekowitz R. A., Whitney C., Wright J., Orkin S. H. Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5215–5219. doi: 10.1073/pnas.85.14.5215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pestka S., Langer J. A., Zoon K. C., Samuel C. E. Interferons and their actions. Annu Rev Biochem. 1987;56:727–777. doi: 10.1146/annurev.bi.56.070187.003455. [DOI] [PubMed] [Google Scholar]
  31. Reich N., Evans B., Levy D., Fahey D., Knight E., Jr, Darnell J. E., Jr Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6394–6398. doi: 10.1073/pnas.84.18.6394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES