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. 1986 Mar;6(3):801–810. doi: 10.1128/mcb.6.3.801

Activation of the human beta-interferon gene requires an interferon-inducible factor.

T Enoch, K Zinn, T Maniatis
PMCID: PMC367580  PMID: 3773893

Abstract

beta-Interferon (beta-IFN) gene expression can be induced by poly(I)-poly(C) or virus, but there is considerable variation in the extent of induction between different cell lines. We characterized two poorly inducible human cell lines, HeLa and 143 thymidine kinase negative (143 tk-), to define cellular factors involved in the activation of the beta-IFN gene. We show that the deficiency in beta-IFN induction in these cells can be complemented by fusion to highly inducible mouse cells. We conclude that the human cells are deficient in a trans-acting factor required for B-IFN gene activation. The level of induction of the beta-IFN gene in HeLa and 143 tk- cells can also be increased by priming with IFN before induction. If IFN priming is carried out in the presence of cycloheximide, a approximately 200-fold increase in induction is observed. We conclude that activation of the beta-IFN gene requires an IFN-inducible factor that is only expressed at low levels in unprimed HeLa and 143 tk- cells.

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Selected References

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  1. Billiau A., Edy V. G., Heremans H., Van Damme J., Desmyter J., Georgiades J. A., De Somer P. Human interferon: mass production in a newly established cell line, MG-63. Antimicrob Agents Chemother. 1977 Jul;12(1):11–15. doi: 10.1128/aac.12.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blau H. M., Chiu C. P., Webster C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell. 1983 Apr;32(4):1171–1180. doi: 10.1016/0092-8674(83)90300-8. [DOI] [PubMed] [Google Scholar]
  3. Bouhnik J., Cassio D., Coezy E., Corvol P., Weiss M. C. Angiotensinogen production by rat hepatoma cells in culture and analysis of its regulation by techniques of somatic cell genetics. J Cell Biol. 1983 Aug;97(2):549–555. doi: 10.1083/jcb.97.2.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brigati D. J., Myerson D., Leary J. J., Spalholz B., Travis S. Z., Fong C. K., Hsiung G. D., Ward D. C. Detection of viral genomes in cultured cells and paraffin-embedded tissue sections using biotin-labeled hybridization probes. Virology. 1983 Apr 15;126(1):32–50. doi: 10.1016/0042-6822(83)90460-9. [DOI] [PubMed] [Google Scholar]
  5. Burke D. C., Ege T., Ringertz N. R. Production of chick interferon by reactivating chick erythrocytes. J Gen Virol. 1980 Oct;50(2):437–440. doi: 10.1099/0022-1317-50-2-437. [DOI] [PubMed] [Google Scholar]
  6. Canaani D., Berg P. Regulated expression of human interferon beta 1 gene after transduction into cultured mouse and rabbit cells. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5166–5170. doi: 10.1073/pnas.79.17.5166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carver D. H., Seto D. S., Migeon B. R. Interferon production and action in mouse, hamster and somatic hybrid mouse-hamster cells. Science. 1968 May 3;160(3827):558–559. doi: 10.1126/science.160.3827.558. [DOI] [PubMed] [Google Scholar]
  8. Cavalieri R. L., Havell E. A., Vilcek J., Pestka S. Induction and decay of human fibroblast interferon mRNA. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4415–4419. doi: 10.1073/pnas.74.10.4415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Cochran B. H., Zullo J., Verma I. M., Stiles C. D. Expression of the c-fos gene and of an fos-related gene is stimulated by platelet-derived growth factor. Science. 1984 Nov 30;226(4678):1080–1082. doi: 10.1126/science.6093261. [DOI] [PubMed] [Google Scholar]
  11. Coghlan J. P., Penschow J. D., Hudson P. J., Niall H. D. Hybridization histochemistry: use of recombinant DNA for tissue localizations of specific mRNA populations. Clin Exp Hypertens A. 1984;6(1-2):63–78. doi: 10.3109/10641968409062551. [DOI] [PubMed] [Google Scholar]
  12. Content J., De Wit L., Tavernier J., Fiers W. Human fibroblast interferon RNA transcripts of different sizes in poly(I).poly(C) induced cells. Nucleic Acids Res. 1983 May 11;11(9):2627–2638. doi: 10.1093/nar/11.9.2627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Content J., Johnston M. I., De Wit L., De Maeyer-Guignard J., De Clercq E. Kinetics and distribution of interferon mRNA in interferon-primed and unprimed mouse L-929 cells. Biochem Biophys Res Commun. 1980 Sep 16;96(1):415–424. doi: 10.1016/0006-291x(80)91231-0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Fujita T., Kohno S. Studies on interferon priming: cellular response to viral and nonviral inducers and requirement of protein synthesis. Virology. 1981 Jul 15;112(1):62–69. doi: 10.1016/0042-6822(81)90612-7. [DOI] [PubMed] [Google Scholar]
  16. Fujita T., Saito S., Kohno S. Priming increases the amount of interferon mRNA in poly(rI).poly(rC)-treated L cells. J Gen Virol. 1979 Nov;45(2):301–308. doi: 10.1099/0022-1317-45-2-301. [DOI] [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. Grodzicker T., Klessig D. F. Expression of unselected adenovirus genes in human cells co-transformed with the HSV-1 tk gene and adenovirus 2 DNA. Cell. 1980 Sep;21(2):453–463. doi: 10.1016/0092-8674(80)90482-1. [DOI] [PubMed] [Google Scholar]
  19. Guggenheim M. A., Friedman R. M., Rabson A. S. Interferon: production by chick erythrocytes activated by cell fusion. Science. 1968 Feb 2;159(3814):542–543. doi: 10.1126/science.159.3814.542. [DOI] [PubMed] [Google Scholar]
  20. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hauser H., Gross G., Bruns W., Hochkeppel H. K., Mayr U., Collins J. Inducibility of human beta-interferon gene in mouse L-cell clones. Nature. 1982 Jun 24;297(5868):650–654. doi: 10.1038/297650a0. [DOI] [PubMed] [Google Scholar]
  22. Havell E. A., Vilcek J. Production of high-titered interferon in cultures of human diploid cells. Antimicrob Agents Chemother. 1972 Dec;2(6):476–484. doi: 10.1128/aac.2.6.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Higashi Y., Sokawa Y., Watanabe Y., Kawade Y., Ohno S., Takaoka C., Taniguchi T. Structure and expression of a cloned cDNA for mouse interferon-beta. J Biol Chem. 1983 Aug 10;258(15):9522–9529. [PubMed] [Google Scholar]
  24. Hiscott J., Cantell K., Weissmann C. Differential expression of human interferon genes. Nucleic Acids Res. 1984 May 11;12(9):3727–3746. doi: 10.1093/nar/12.9.3727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kelley K. A., Pitha P. M. Characterization of a mouse interferon gene locus II. Differential expression of alpha-interferon genes. Nucleic Acids Res. 1985 Feb 11;13(3):825–839. doi: 10.1093/nar/13.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
  27. Killary A. M., Fournier R. E. A genetic analysis of extinction: trans-dominant loci regulate expression of liver-specific traits in hepatoma hybrid cells. Cell. 1984 Sep;38(2):523–534. doi: 10.1016/0092-8674(84)90507-5. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Maroteaux L., Kahana C., Mory Y., Groner Y., Revel M. Sequences involved in the regulated expression of the human interferon-beta1 gene in recombinant SV40 DNA vectors replicating in monkey cells. EMBO J. 1983;2(3):325–332. doi: 10.1002/j.1460-2075.1983.tb01426.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Nir U., Cohen B., Chen L., Revel M. A human IFN-beta 1 gene deleted of promoter sequences upstream from the TATA box is controlled post-transcriptionally by dsRNA. Nucleic Acids Res. 1984 Sep 25;12(18):6979–6993. doi: 10.1093/nar/12.18.6979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ohno S., Taniguchi T. The 5'-flanking sequence of human interferon-beta 1 gene is responsible for viral induction of transcription. Nucleic Acids Res. 1983 Aug 25;11(16):5403–5412. doi: 10.1093/nar/11.16.5403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Raj N. B., Pitha P. M. Two levels of regulation of beta-interferon gene expression in human cells. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3923–3927. doi: 10.1073/pnas.80.13.3923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schneiderman S., Farber J. L., Baserga R. A simple method for decreasing the toxicity of polyethylene glycol in mammalian cell hybridization. Somatic Cell Genet. 1979 Mar;5(2):263–269. doi: 10.1007/BF01539165. [DOI] [PubMed] [Google Scholar]
  36. Sehgal P. B., Dobberstein B., Tamm I. Interferon messenger RNA content of human fibroblasts during induction, shutoff, and superinduction of interferon production. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3409–3413. doi: 10.1073/pnas.74.8.3409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  38. Stein G. H., Yanishevsky R. Autoradiography. Methods Enzymol. 1979;58:279–292. doi: 10.1016/s0076-6879(79)58143-9. [DOI] [PubMed] [Google Scholar]
  39. Steward W. E., 2nd, Gosser L. B., Lockart R. Z., Jr The effect of priming with interferon on interferon production by two lines of L cells. J Gen Virol. 1972 Apr;15(1):85–87. doi: 10.1099/0022-1317-15-1-85. [DOI] [PubMed] [Google Scholar]
  40. Stewart W. E., 2nd, Gosser L. B., Lockart R. Z., Jr Priming: a nonantiviral function of interferon. J Virol. 1971 Jun;7(6):792–801. doi: 10.1128/jvi.7.6.792-801.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tan Y. H., Berthold W. A mechanism for the induction and regulation of human fibroblastoid interferon genetic expression. J Gen Virol. 1977 Mar;34(3):401–411. doi: 10.1099/0022-1317-34-3-401. [DOI] [PubMed] [Google Scholar]
  42. Tomkins G. M., Levinson B. B., Baxter J. D., Dethlefsen L. Further evidence for posttranscriptional control of inducible tyrosine aminotransferase synthesis in cultured hepatoma cells. Nat New Biol. 1972 Sep 6;239(88):9–14. doi: 10.1038/newbio239009a0. [DOI] [PubMed] [Google Scholar]
  43. Wigler M., Sweet R., Sim G. K., Wold B., Pellicer A., Lacy E., Maniatis T., Silverstein S., Axel R. Transformation of mammalian cells with genes from procaryotes and eucaryotes. Cell. 1979 Apr;16(4):777–785. doi: 10.1016/0092-8674(79)90093-x. [DOI] [PubMed] [Google Scholar]
  44. Yamamoto K. R., Gehring U., Stampfer M. R., Sibley C. H. Genetic approaches to steroid hormone action. Recent Prog Horm Res. 1976;32:3–32. doi: 10.1016/b978-0-12-571132-6.50008-7. [DOI] [PubMed] [Google Scholar]
  45. Zawatzky R., De Maeyer E., De Maeyer-Guignard J. Identification of individual interferon-producing cells by in situ hybridization. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1136–1140. doi: 10.1073/pnas.82.4.1136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]
  47. Zinn K., Mellon P., Ptashne M., Maniatis T. Regulated expression of an extrachromosomal human beta-interferon gene in mouse cells. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4897–4901. doi: 10.1073/pnas.79.16.4897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Zwarthoff E. C., Mooren A. T., Trapman J. Organization, structure and expression of murine interferon alpha genes. Nucleic Acids Res. 1985 Feb 11;13(3):791–804. doi: 10.1093/nar/13.3.791. [DOI] [PMC free article] [PubMed] [Google Scholar]

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