Skip to main content
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
. 1992 Mar 15;89(6):2150–2154. doi: 10.1073/pnas.89.6.2150

An ATF/CREB binding site is required for virus induction of the human interferon beta gene [corrected]

W Du 1, T Maniatis 1
PMCID: PMC48614  PMID: 1532252

Abstract

We report the characterization of a distinct regulatory element of the human interferon beta (HuIFN-beta) gene promoter, which we designate PRDIV (positive regulatory domain IV). In previous studies, sequences between -104 and -91 base pairs upstream from the start site of transcription were shown to be required for maximal levels of virus induction in mouse L929 cells. We have localized the essential sequence in this region extending from -99 to at least -91, and we show that this sequence is a binding site for a protein of the activating transcription factor/cAMP response element binding protein (ATF/CREB) family of transcription factors. Mutations in PRDIV that decrease the affinity of one member of this family (ATF-2/CRE-BP1) decrease the level of virus induction in vivo. Moreover, multiple copies of PRDIV can confer both virus and cAMP inducibility upon a minimal promoter in L929 cells, while it is constitutively active in HeLa cells. We conclude that PRDIV is a distinct regulatory element of the HuIFN-beta promoter and that the signal transduction pathways involved in virus and cAMP induction may partially overlap.

Full text

PDF
2151

Images in this article

Selected References

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

  1. Benbrook D. M., Jones N. C. Heterodimer formation between CREB and JUN proteins. Oncogene. 1990 Mar;5(3):295–302. [PubMed] [Google Scholar]
  2. Boshart M., Weih F., Schmidt A., Fournier R. E., Schütz G. A cyclic AMP response element mediates repression of tyrosine aminotransferase gene transcription by the tissue-specific extinguisher locus Tse-1. Cell. 1990 Jun 1;61(5):905–916. doi: 10.1016/0092-8674(90)90201-o. [DOI] [PubMed] [Google Scholar]
  3. Chen C. A., Okayama H. Calcium phosphate-mediated gene transfer: a highly efficient transfection system for stably transforming cells with plasmid DNA. Biotechniques. 1988 Jul-Aug;6(7):632–638. [PubMed] [Google Scholar]
  4. 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]
  5. Fujita T., Miyamoto M., Kimura Y., Hammer J., Taniguchi T. Involvement of a cis-element that binds an H2TF-1/NF kappa B like factor(s) in the virus-induced interferon-beta gene expression. Nucleic Acids Res. 1989 May 11;17(9):3335–3346. doi: 10.1093/nar/17.9.3335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fujita T., Ohno S., Yasumitsu H., Taniguchi T. Delimitation and properties of DNA sequences required for the regulated expression of human interferon-beta gene. Cell. 1985 Jun;41(2):489–496. doi: 10.1016/s0092-8674(85)80022-2. [DOI] [PubMed] [Google Scholar]
  7. Fujita T., Sakakibara J., Sudo Y., Miyamoto M., Kimura Y., Taniguchi T. Evidence for a nuclear factor(s), IRF-1, mediating induction and silencing properties to human IFN-beta gene regulatory elements. EMBO J. 1988 Nov;7(11):3397–3405. doi: 10.1002/j.1460-2075.1988.tb03213.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fujita T., Shibuya H., Hotta H., Yamanishi K., Taniguchi T. Interferon-beta gene regulation: tandemly repeated sequences of a synthetic 6 bp oligomer function as a virus-inducible enhancer. Cell. 1987 May 8;49(3):357–367. doi: 10.1016/0092-8674(87)90288-1. [DOI] [PubMed] [Google Scholar]
  9. García-Blanco M. A., Clerc R. G., Sharp P. A. The DNA-binding homeo domain of the Oct-2 protein. Genes Dev. 1989 Jun;3(6):739–745. doi: 10.1101/gad.3.6.739. [DOI] [PubMed] [Google Scholar]
  10. Goldfeld A. E., Doyle C., Maniatis T. Human tumor necrosis factor alpha gene regulation by virus and lipopolysaccharide. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9769–9773. doi: 10.1073/pnas.87.24.9769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goodbourn S., Burstein H., Maniatis T. The human beta-interferon gene enhancer is under negative control. Cell. 1986 May 23;45(4):601–610. doi: 10.1016/0092-8674(86)90292-8. [DOI] [PubMed] [Google Scholar]
  12. Goodbourn S., Maniatis T. Overlapping positive and negative regulatory domains of the human beta-interferon gene. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1447–1451. doi: 10.1073/pnas.85.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Hai T. W., Liu F., Coukos W. J., Green M. R. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989 Dec;3(12B):2083–2090. doi: 10.1101/gad.3.12b.2083. [DOI] [PubMed] [Google Scholar]
  15. Hai T., Curran T. Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3720–3724. doi: 10.1073/pnas.88.9.3720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Harada H., Willison K., Sakakibara J., Miyamoto M., Fujita T., Taniguchi T. Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell. 1990 Oct 19;63(2):303–312. doi: 10.1016/0092-8674(90)90163-9. [DOI] [PubMed] [Google Scholar]
  17. Hiscott J., Alper D., Cohen L., Leblanc J. F., Sportza L., Wong A., Xanthoudakis S. Induction of human interferon gene expression is associated with a nuclear factor that interacts with the NF-kappa B site of the human immunodeficiency virus enhancer. J Virol. 1989 Jun;63(6):2557–2566. doi: 10.1128/jvi.63.6.2557-2566.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hubbell H. R., Boyer J. E., Roane P., Burch R. M. Cyclic AMP mediates the direct antiproliferative action of mismatched double-stranded RNA. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):906–910. doi: 10.1073/pnas.88.3.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Keller A. D., Maniatis T. Identification of an inducible factor that binds to a positive regulatory element of the human beta-interferon gene. Proc Natl Acad Sci U S A. 1988 May;85(10):3309–3313. doi: 10.1073/pnas.85.10.3309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kuga T., Fujita T., Taniguchi T. Nucleotide sequence of the mouse interferon-beta gene. Nucleic Acids Res. 1989 Apr 25;17(8):3291–3291. doi: 10.1093/nar/17.8.3291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Leblanc J. F., Cohen L., Rodrigues M., Hiscott J. Synergism between distinct enhanson domains in viral induction of the human beta interferon gene. Mol Cell Biol. 1990 Aug;10(8):3987–3993. doi: 10.1128/mcb.10.8.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lenardo M. J., Fan C. M., Maniatis T., Baltimore D. The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction. Cell. 1989 Apr 21;57(2):287–294. doi: 10.1016/0092-8674(89)90966-5. [DOI] [PubMed] [Google Scholar]
  23. Lillie J. W., Green M. R. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. doi: 10.1038/338039a0. [DOI] [PubMed] [Google Scholar]
  24. Lin Y. S., Green M. R. Interaction of a common cellular transcription factor, ATF, with regulatory elements in both E1a- and cyclic AMP-inducible promoters. Proc Natl Acad Sci U S A. 1988 May;85(10):3396–3400. doi: 10.1073/pnas.85.10.3396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Liu F., Green M. R. A specific member of the ATF transcription factor family can mediate transcription activation by the adenovirus E1a protein. Cell. 1990 Jun 29;61(7):1217–1224. doi: 10.1016/0092-8674(90)90686-9. [DOI] [PubMed] [Google Scholar]
  26. MacDonald N. J., Kuhl D., Maguire D., Näf D., Gallant P., Goswamy A., Hug H., Büeler H., Chaturvedi M., de la Fuente J. Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes. Cell. 1990 Mar 9;60(5):767–779. doi: 10.1016/0092-8674(90)90091-r. [DOI] [PubMed] [Google Scholar]
  27. Maekawa T., Sakura H., Kanei-Ishii C., Sudo T., Yoshimura T., Fujisawa J., Yoshida M., Ishii S. Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain. EMBO J. 1989 Jul;8(7):2023–2028. doi: 10.1002/j.1460-2075.1989.tb03610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi: 10.1016/s0092-8674(88)91307-4. [DOI] [PubMed] [Google Scholar]
  29. Montminy M. R., Sevarino K. A., Wagner J. A., Mandel G., Goodman R. H. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6682–6686. doi: 10.1073/pnas.83.18.6682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shaw P. E., Schröter H., Nordheim A. The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter. Cell. 1989 Feb 24;56(4):563–572. doi: 10.1016/0092-8674(89)90579-5. [DOI] [PubMed] [Google Scholar]
  31. Shirakawa F., Mizel S. B. In vitro activation and nuclear translocation of NF-kappa B catalyzed by cyclic AMP-dependent protein kinase and protein kinase C. Mol Cell Biol. 1989 Jun;9(6):2424–2430. doi: 10.1128/mcb.9.6.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Studier F. W., Moffatt B. A. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol. 1986 May 5;189(1):113–130. doi: 10.1016/0022-2836(86)90385-2. [DOI] [PubMed] [Google Scholar]
  33. Visvanathan K. V., Goodbourn S. Double-stranded RNA activates binding of NF-kappa B to an inducible element in the human beta-interferon promoter. EMBO J. 1989 Apr;8(4):1129–1138. doi: 10.1002/j.1460-2075.1989.tb03483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Xanthoudakis S., Cohen L., Hiscott J. Multiple protein-DNA interactions within the human interferon-beta regulatory element. J Biol Chem. 1989 Jan 15;264(2):1139–1145. [PubMed] [Google Scholar]
  35. 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]

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