Abstract
The interferon (IFN)-activated human 2',5'-oligo(A) synthetase E gene contains 11 RNA starts and lacks TATA and CAAT signals. DNA sequences around the promoter make the expression of the chloramphenicol acetyltransferase gene (CAT) inducible over 20-fold by IFN. A 72-base-pair segment (E-IRS) immediately upstream of the RNA starts was defined as being required for IFN-activated expression of the E-gene promoter-CAT constructs and acts in a position-independent manner. It also confers IFN-activated enhancement to the herpes simplex virus thymidine kinase promoter. On this promoter, the 5' part of the E-IRS functions as a constitutive enhancer, while the last 16 base pairs of the E-IRS is sufficient to give IFN-induced expression. On the E-gene promoter, the constitutive enhancer and the IFN-activated sequence are both needed but can be separated. In addition, promoter competition experiments indicate a third regulatory region which helps to repress expression of the E gene in uninduced cells.
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aguet M., Mogensen K. E. Interferon receptors. Interferon. 1983;5:1–22. [PubMed] [Google Scholar]
- 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]
- 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]
- Chernajovsky Y., Mory Y., Chen L., Marks Z., Novick D., Rubinstein M., Revel M. Efficient constitutive production of human fibroblast interferon by hamster cells transformed with the IFN-beta 1 gene fused to an SV40 early promoter. DNA. 1984 Aug;3(4):297–308. doi: 10.1089/dna.1.1984.3.297. [DOI] [PubMed] [Google Scholar]
- De Benedetti A., Pytel B. A., Baglioni C. Loss of (2'-5')oligoadenylate synthetase activity by production of antisense RNA results in lack of protection by interferon from viral infections. Proc Natl Acad Sci U S A. 1987 Feb;84(3):658–662. doi: 10.1073/pnas.84.3.658. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- Falkner F. G., Zachau H. G. Correct transcription of an immunoglobulin kappa gene requires an upstream fragment containing conserved sequence elements. Nature. 1984 Jul 5;310(5972):71–74. doi: 10.1038/310071a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Fellous M., Nir U., Wallach D., Merlin G., Rubinstein M., Revel M. Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells. Proc Natl Acad Sci U S A. 1982 May;79(10):3082–3086. doi: 10.1073/pnas.79.10.3082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Ghosh P. K., Reddy V. B., Swinscoe J., Lebowitz P., Weissman S. M. Heterogeneity and 5'-terminal structures of the late RNAs of simian virus 40. J Mol Biol. 1978 Dec 25;126(4):813–846. doi: 10.1016/0022-2836(78)90022-0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Klein-Hitpass L., Schorpp M., Wagner U., Ryffel G. U. An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell. 1986 Sep 26;46(7):1053–1061. doi: 10.1016/0092-8674(86)90705-1. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
- Nir U., Walker M. D., Rutter W. J. Regulation of rat insulin 1 gene expression: evidence for negative regulation in nonpancreatic cells. Proc Natl Acad Sci U S A. 1986 May;83(10):3180–3184. doi: 10.1073/pnas.83.10.3180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reynolds G. A., Basu S. K., Osborne T. F., Chin D. J., Gil G., Brown M. S., Goldstein J. L., Luskey K. L. HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions. Cell. 1984 Aug;38(1):275–285. doi: 10.1016/0092-8674(84)90549-x. [DOI] [PubMed] [Google Scholar]
- Samanta H., Engel D. A., Chao H. M., Thakur A., García-Blanco M. A., Lengyel P. Interferons as gene activators. Cloning of the 5' terminus and the control segment of an interferon activated gene. J Biol Chem. 1986 Sep 5;261(25):11849–11858. [PubMed] [Google Scholar]
- 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]
- Weiher H., König M., Gruss P. Multiple point mutations affecting the simian virus 40 enhancer. Science. 1983 Feb 11;219(4585):626–631. doi: 10.1126/science.6297005. [DOI] [PubMed] [Google Scholar]