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. 1988 Mar;7(3):751–759. doi: 10.1002/j.1460-2075.1988.tb02872.x

Interferon-induced binding of nuclear factors to promoter elements of the 2-5A synthetase gene.

M N Rutherford 1, G E Hannigan 1, B R Williams 1
PMCID: PMC454386  PMID: 2456211

Abstract

Fragments of the 5'-flanking sequence of a human 2-5A synthetase gene were assayed for their ability to respond to interferon-alpha (IFN). Transient transfection assays in monkey cells demonstrated that the 5' boundary of the sequence required for IFN-regulated transcription is, at most, 155 nucleotides upstream from the presumed translational initiation codon. The 3' boundary of this sequence lies within a region of multiple transcription start sites preceded by no obvious TATA box. Binding assays, using a 40-bp probe derived from this IFN-responsive sequence, demonstrated the presence of three IFN-modulated, DNA-factor band shifts using nuclear extracts prepared from human and monkey cells. The induction of these complexes in human cells by IFN occurs with kinetics which closely parallel those previously observed for the transcriptional activation of the 2-5A synthetase gene by IFN. In vivo competition assays showed that the same 40-bp region which bound IFN-modulated factors could decrease the IFN-induced activity of a co-transfected 2-5A synthetase promoter; this fragment, regardless of its orientation, could confer IFN-inducibility on a heterologous promoter.

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Selected References

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

  1. Benech P., Merlin G., Revel M., Chebath J. 3' end structure of the human (2'-5') oligo A synthetase gene: prediction of two distinct proteins with cell type-specific expression. Nucleic Acids Res. 1985 Feb 25;13(4):1267–1281. doi: 10.1093/nar/13.4.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benech P., Mory Y., Revel M., Chebath J. Structure of two forms of the interferon-induced (2'-5') oligo A synthetase of human cells based on cDNAs and gene sequences. EMBO J. 1985 Sep;4(9):2249–2256. doi: 10.1002/j.1460-2075.1985.tb03922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carthew R. W., Chodosh L. A., Sharp P. A. An RNA polymerase II transcription factor binds to an upstream element in the adenovirus major late promoter. Cell. 1985 Dec;43(2 Pt 1):439–448. doi: 10.1016/0092-8674(85)90174-6. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Faltynek C. R., McCandless S., Chebath J., Baglioni C. Different mechanisms for activation of gene transcription by interferons alpha and gamma. Virology. 1985 Jul 15;144(1):173–180. doi: 10.1016/0042-6822(85)90315-0. [DOI] [PubMed] [Google Scholar]
  7. Fried M., Crothers D. M. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981 Dec 11;9(23):6505–6525. doi: 10.1093/nar/9.23.6505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Friedman R. L., Stark G. R. alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature. 1985 Apr 18;314(6012):637–639. doi: 10.1038/314637a0. [DOI] [PubMed] [Google Scholar]
  10. Garner M. M., Revzin A. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res. 1981 Jul 10;9(13):3047–3060. doi: 10.1093/nar/9.13.3047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  13. Hall C. V., Jacob P. E., Ringold G. M., Lee F. Expression and regulation of Escherichia coli lacZ gene fusions in mammalian cells. J Mol Appl Genet. 1983;2(1):101–109. [PubMed] [Google Scholar]
  14. Hannigan G., Williams B. R. Transcriptional regulation of interferon-responsive genes is closely linked to interferon receptor occupancy. EMBO J. 1986 Jul;5(7):1607–1613. doi: 10.1002/j.1460-2075.1986.tb04403.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. 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]
  18. Kelly J. M., Porter A. C., Chernajovsky Y., Gilbert C. S., Stark G. R., Kerr I. M. Characterization of a human gene inducible by alpha- and beta-interferons and its expression in mouse cells. EMBO J. 1986 Jul;5(7):1601–1606. doi: 10.1002/j.1460-2075.1986.tb04402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Kohase M., May L. T., Tamm I., Vilcek J., Sehgal P. B. A cytokine network in human diploid fibroblasts: interactions of beta-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1. Mol Cell Biol. 1987 Jan;7(1):273–280. doi: 10.1128/mcb.7.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Korber B., Hood L., Stroynowski I. Regulation of murine class I genes by interferons is controlled by regions located both 5' and 3' to the transcription initiation site. Proc Natl Acad Sci U S A. 1987 May;84(10):3380–3384. doi: 10.1073/pnas.84.10.3380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kusari J., Sen G. C. Transcriptional analyses of interferon-inducible mRNAs. Mol Cell Biol. 1987 Jan;7(1):528–531. doi: 10.1128/mcb.7.1.528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Luster A. D., Ravetch J. V. Genomic characterization of a gamma-interferon-inducible gene (IP-10) and identification of an interferon-inducible hypersensitive site. Mol Cell Biol. 1987 Oct;7(10):3723–3731. doi: 10.1128/mcb.7.10.3723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  28. McMahon M., Stark G. R., Kerr I. M. Interferon-induced gene expression in wild-type and interferon-resistant human lymphoblastoid (Daudi) cells. J Virol. 1986 Jan;57(1):362–366. doi: 10.1128/jvi.57.1.362-366.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  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. Porter A. C., Chernajovsky Y., Dale T. C., Gilbert C. S., Stark G. R., Kerr I. M. Interferon response element of the human gene 6-16. EMBO J. 1988 Jan;7(1):85–92. doi: 10.1002/j.1460-2075.1988.tb02786.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Resnitzky D., Yarden A., Zipori D., Kimchi A. Autocrine beta-related interferon controls c-myc suppression and growth arrest during hematopoietic cell differentiation. Cell. 1986 Jul 4;46(1):31–40. doi: 10.1016/0092-8674(86)90857-3. [DOI] [PubMed] [Google Scholar]
  34. Saunders M. E., Gewert D. R., Tugwell M. E., McMahon M., Williams B. R. Human 2-5A synthetase: characterization of a novel cDNA and corresponding gene structure. EMBO J. 1985 Jul;4(7):1761–1768. doi: 10.1002/j.1460-2075.1985.tb03848.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shiojiri S., Fukunaga R., Ichii Y., Sokawa Y. Structure and expression of a cloned cDNA for human (2'-5')oligoadenylate synthetase. J Biochem. 1986 May;99(5):1455–1464. doi: 10.1093/oxfordjournals.jbchem.a135615. [DOI] [PubMed] [Google Scholar]
  36. Sleigh M. J. A nonchromatographic assay for expression of the chloramphenicol acetyltransferase gene in eucaryotic cells. Anal Biochem. 1986 Jul;156(1):251–256. doi: 10.1016/0003-2697(86)90180-6. [DOI] [PubMed] [Google Scholar]
  37. Sugita K., Miyazaki J., Appella E., Ozato K. Interferons increase transcription of a major histocompatibility class I gene via a 5' interferon consensus sequence. Mol Cell Biol. 1987 Jul;7(7):2625–2630. doi: 10.1128/mcb.7.7.2625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Südhof T. C., Van der Westhuyzen D. R., Goldstein J. L., Brown M. S., Russell D. W. Three direct repeats and a TATA-like sequence are required for regulated expression of the human low density lipoprotein receptor gene. J Biol Chem. 1987 Aug 5;262(22):10773–10779. [PubMed] [Google Scholar]
  39. Wathelet M., Moutschen S., Cravador A., DeWit L., Defilippi P., Huez G., Content J. Full-length sequence and expression of the 42 kDa 2-5A synthetase induced by human interferon. FEBS Lett. 1986 Feb 3;196(1):113–120. doi: 10.1016/0014-5793(86)80224-1. [DOI] [PubMed] [Google Scholar]
  40. Williams B. R., Saunders M. E., Willard H. F. Interferon-regulated human 2-5A synthetase gene maps to chromosome 12. Somat Cell Mol Genet. 1986 Jul;12(4):403–408. doi: 10.1007/BF01570735. [DOI] [PubMed] [Google Scholar]
  41. Wong G. H., Goeddel D. V. Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. 1986 Oct 30-Nov 5Nature. 323(6091):819–822. doi: 10.1038/323819a0. [DOI] [PubMed] [Google Scholar]
  42. Yap W. H., Teo T. S., Tan Y. H. An early event in the interferon-induced transmembrane signaling process. Science. 1986 Oct 17;234(4774):355–358. doi: 10.1126/science.2429366. [DOI] [PubMed] [Google Scholar]
  43. Zullo J. N., Cochran B. H., Huang A. S., Stiles C. D. Platelet-derived growth factor and double-stranded ribonucleic acids stimulate expression of the same genes in 3T3 cells. Cell. 1985 Dec;43(3 Pt 2):793–800. doi: 10.1016/0092-8674(85)90252-1. [DOI] [PubMed] [Google Scholar]

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