Abstract
We have performed a functional analysis of DNA sequences upstream from the gene for IE mRNA3 of herpes simplex virus type 1. Nucleotide sequences involved in initiation and positive regulation of transcription have been defined by construction of specific deletions in vitro. Transcription was assayed in vivo by microinjection into Xenopus oocytes, or by introduction of plasmid DNA into tissue culture cells and measurement of transient expression. Three functional promoter elements have been defined: i) Sequences between -16 and -37 which are not essential for transcription but are required for accurate initiation. ii) Proximal promoter sequences which are sufficient for transcription initiation in the absence of upstream sequences. iii) Far-upstream promoter sequences (more than 108bp upstream) which increase transcription in oocytes, and contain positive regulatory sequences (-174 to -331) which respond strongly to a factor in the virus inoculum.
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Selected References
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- Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. doi: 10.1016/0092-8674(81)90413-x. [DOI] [PubMed] [Google Scholar]
- Benoist C., Chambon P. In vivo sequence requirements of the SV40 early promotor region. Nature. 1981 Mar 26;290(5804):304–310. doi: 10.1038/290304a0. [DOI] [PubMed] [Google Scholar]
- Benoist C., O'Hare K., Breathnach R., Chambon P. The ovalbumin gene-sequence of putative control regions. Nucleic Acids Res. 1980 Jan 11;8(1):127–142. doi: 10.1093/nar/8.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berk A. J., Sharp P. A. Spliced early mRNAs of simian virus 40. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1274–1278. doi: 10.1073/pnas.75.3.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brinster R. L., Chen H. Y., Warren R., Sarthy A., Palmiter R. D. Regulation of metallothionein--thymidine kinase fusion plasmids injected into mouse eggs. Nature. 1982 Mar 4;296(5852):39–42. doi: 10.1038/296039a0. [DOI] [PubMed] [Google Scholar]
- Capecchi M. R. High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell. 1980 Nov;22(2 Pt 2):479–488. doi: 10.1016/0092-8674(80)90358-x. [DOI] [PubMed] [Google Scholar]
- Clements J. B., Watson R. J., Wilkie N. M. Temporal regulation of herpes simplex virus type 1 transcription: location of transcripts on the viral genome. Cell. 1977 Sep;12(1):275–285. doi: 10.1016/0092-8674(77)90205-7. [DOI] [PubMed] [Google Scholar]
- Cordingley M. G., Preston C. M. Transcription and translation of the herpes simplex virus type 1 thymidine kinase gene after microinjection into Xenopus laevis oocytes. J Gen Virol. 1981 Jun;54(Pt 2):409–414. doi: 10.1099/0022-1317-54-2-409. [DOI] [PubMed] [Google Scholar]
- Costanzo F., Campadelli-Fiume G., Foa-Tomasi L., Cassai E. Evidence that herpes simplex virus DNA is transcribed by cellular RNA polymerase B. J Virol. 1977 Mar;21(3):996–1001. doi: 10.1128/jvi.21.3.996-1001.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dhar R., McClements W. L., Enquist L. W., Vande Woude G. F. Nucleotide sequences of integrated Moloney sarcoma provirus long terminal repeats and their host and viral junctions. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3937–3941. doi: 10.1073/pnas.77.7.3937. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham F. L., Veldhuisen G., Wilkie N. M. Infectious herpesvirus DNA. Nat New Biol. 1973 Oct 31;245(148):265–266. doi: 10.1038/newbio245265a0. [DOI] [PubMed] [Google Scholar]
- Grosschedl R., Birnstiel M. L. Identification of regulatory sequences in the prelude sequences of an H2A histone gene by the study of specific deletion mutants in vivo. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1432–1436. doi: 10.1073/pnas.77.3.1432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grosveld G. C., Rosenthal A., Flavell R. A. Sequence requirements for the transcription of the rabbit beta-globin gene in vivo: the -80 region. Nucleic Acids Res. 1982 Aug 25;10(16):4951–4971. doi: 10.1093/nar/10.16.4951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grosveld G. C., de Boer E., Shewmaker C. K., Flavell R. A. DNA sequences necessary for transcription of the rabbit beta-globin gene in vivo. Nature. 1982 Jan 14;295(5845):120–126. doi: 10.1038/295120a0. [DOI] [PubMed] [Google Scholar]
- Gurdon J. B. Injected nuclei in frog oocytes: fate, enlargement, and chromatin dispersal. J Embryol Exp Morphol. 1976 Dec;36(3):523–540. [PubMed] [Google Scholar]
- Jamieson A. T., Subak-Sharpe J. H. Biochemical studies on the herpes simplex virus-specified deoxypyrimidine kinase activity. J Gen Virol. 1974 Sep;24(3):481–492. doi: 10.1099/0022-1317-24-3-481. [DOI] [PubMed] [Google Scholar]
- Jones P. C., Roizman B. Regulation of herpesvirus macromolecular synthesis. VIII. The transcription program consists of three phases during which both extent of transcription and accumulation of RNA in the cytoplasm are regulated. J Virol. 1979 Aug;31(2):299–314. doi: 10.1128/jvi.31.2.299-314.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozak M., Roizman B. Regulation of herpesvirus macromolecular synthesis: nuclear retention of nontranslated viral RNA sequences. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4322–4326. doi: 10.1073/pnas.71.11.4322. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leiden J. M., Buttyan R., Spear P. G. Herpes simplex virus gene expression in transformed cells. I. Regulation of the viral thymidine kinase gene in transformed L cells by products of superinfecting virus. J Virol. 1976 Nov;20(2):413–424. doi: 10.1128/jvi.20.2.413-424.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leung W. C., Dimock K., Smiley J. R., Bacchetti S. Herpes simplex virus thymidine kinase transcripts are absent from both nucleus and cytoplasm during infection in the presence of cycloheximide. J Virol. 1980 Nov;36(2):361–365. doi: 10.1128/jvi.36.2.361-365.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lilley D. M. The inverted repeat as a recognizable structural feature in supercoiled DNA molecules. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6468–6472. doi: 10.1073/pnas.77.11.6468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackem S., Roizman B. Differentiation between alpha promoter and regulator regions of herpes simplex virus 1: the functional domains and sequence of a movable alpha regulator. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4917–4921. doi: 10.1073/pnas.79.16.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackem S., Roizman B. Regulation of alpha genes of herpes simplex virus: the alpha 27 gene promoter-thymidine kinase chimera is positively regulated in converted L cells. J Virol. 1982 Sep;43(3):1015–1023. doi: 10.1128/jvi.43.3.1015-1023.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackem S., Roizman B. Regulation of herpesvirus macromolecular synthesis: transcription-initiation sites and domains of alpha genes. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7122–7126. doi: 10.1073/pnas.77.12.7122. [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]
- McKnight S. L., Gavis E. R., Kingsbury R., Axel R. Analysis of transcriptional regulatory signals of the HSV thymidine kinase gene: identification of an upstream control region. Cell. 1981 Aug;25(2):385–398. doi: 10.1016/0092-8674(81)90057-x. [DOI] [PubMed] [Google Scholar]
- McKnight S. L., Kingsbury R. Transcriptional control signals of a eukaryotic protein-coding gene. Science. 1982 Jul 23;217(4557):316–324. doi: 10.1126/science.6283634. [DOI] [PubMed] [Google Scholar]
- Mellon P., Parker V., Gluzman Y., Maniatis T. Identification of DNA sequences required for transcription of the human alpha 1-globin gene in a new SV40 host-vector system. Cell. 1981 Dec;27(2 Pt 1):279–288. doi: 10.1016/0092-8674(81)90411-6. [DOI] [PubMed] [Google Scholar]
- Murchie M. J., McGeoch D. J. DNA sequence analysis of an immediate-early gene region of the herpes simplex virus type 1 genome (map coordinates 0.950 to 0.978). J Gen Virol. 1982 Sep;62(Pt 1):1–15. doi: 10.1099/0022-1317-62-1-1. [DOI] [PubMed] [Google Scholar]
- Notarianni E. L., Preston C. M. Activation of cellular stress protein genes by herpes simplex virus temperature-sensitive mutants which overproduce immediate early polypeptides. Virology. 1982 Nov;123(1):113–122. doi: 10.1016/0042-6822(82)90299-9. [DOI] [PubMed] [Google Scholar]
- Panayotatos N., Wells R. D. Cruciform structures in supercoiled DNA. Nature. 1981 Feb 5;289(5797):466–470. doi: 10.1038/289466a0. [DOI] [PubMed] [Google Scholar]
- Pelham H. R. A regulatory upstream promoter element in the Drosophila hsp 70 heat-shock gene. Cell. 1982 Sep;30(2):517–528. doi: 10.1016/0092-8674(82)90249-5. [DOI] [PubMed] [Google Scholar]
- Pellicer A., Robins D., Wold B., Sweet R., Jackson J., Lowy I., Roberts J. M., Sim G. K., Silverstein S., Axel R. Altering genotype and phenotype by DNA-mediated gene transfer. Science. 1980 Sep 19;209(4463):1414–1422. doi: 10.1126/science.7414320. [DOI] [PubMed] [Google Scholar]
- Post L. E., Mackem S., Roizman B. Regulation of alpha genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with alpha gene promoters. Cell. 1981 May;24(2):555–565. doi: 10.1016/0092-8674(81)90346-9. [DOI] [PubMed] [Google Scholar]
- Preston C. M. Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK. J Virol. 1979 Jan;29(1):275–284. doi: 10.1128/jvi.29.1.275-284.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Preston C. M. The cell-free synthesis of herpesvirus-induced polypeptides. Virology. 1977 May 1;78(1):349–353. doi: 10.1016/0042-6822(77)90109-x. [DOI] [PubMed] [Google Scholar]
- Proudfoot N. J. Eukaryotic promoters? Nature. 1979 May 31;279(5712):376–376. doi: 10.1038/279376a0. [DOI] [PubMed] [Google Scholar]
- Rixon F. J., Campbell M. E., Clements J. B. The immediate-early mRNA that encodes the regulatory polypeptide Vmw 175 of herpes simplex virus type 1 is unspliced. EMBO J. 1982;1(10):1273–1277. doi: 10.1002/j.1460-2075.1982.tb00024.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SZYBALSKA E. H., SZYBALSKI W. Genetics of human cess line. IV. DNA-mediated heritable transformation of a biochemical trait. Proc Natl Acad Sci U S A. 1962 Dec 15;48:2026–2034. doi: 10.1073/pnas.48.12.2026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakonju S., Bogenhagen D. F., Brown D. D. A control region in the center of the 5S RNA gene directs specific initiation of transcription: I. The 5' border of the region. Cell. 1980 Jan;19(1):13–25. doi: 10.1016/0092-8674(80)90384-0. [DOI] [PubMed] [Google Scholar]
- Stow N. D., Wilkie N. M. An improved technique for obtaining enhanced infectivity with herpes simplex virus type 1 DNA. J Gen Virol. 1976 Dec;33(3):447–458. doi: 10.1099/0022-1317-33-3-447. [DOI] [PubMed] [Google Scholar]
- Swanstrom R. I., Wagner E. K. Regulation of synthesis of herpes simplex type 1 virus mRNA during productive infection. Virology. 1974 Aug;60(2):522–533. doi: 10.1016/0042-6822(74)90346-8. [DOI] [PubMed] [Google Scholar]
- Twigg A. J., Sherratt D. Trans-complementable copy-number mutants of plasmid ColE1. Nature. 1980 Jan 10;283(5743):216–218. doi: 10.1038/283216a0. [DOI] [PubMed] [Google Scholar]
- Watson R. J., Clements J. B. A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis. Nature. 1980 May 29;285(5763):329–330. doi: 10.1038/285329a0. [DOI] [PubMed] [Google Scholar]
- Watson R. J., Vande Woude G. F. DNA sequence of an immediate-early gene (IEmRNA-5) of herpes simplex virus type I. Nucleic Acids Res. 1982 Feb 11;10(3):979–991. doi: 10.1093/nar/10.3.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weaver R. F., Weissmann C. Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. Nucleic Acids Res. 1979 Nov 10;7(5):1175–1193. doi: 10.1093/nar/7.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilkie N. M., Clements J. B., Boll W., Mantei N., Lonsdale D., Weissmann C. Hybrid plasmids containing an active thymidine kinase gene of Herpes simplex virus 1. Nucleic Acids Res. 1979 Oct 25;7(4):859–877. doi: 10.1093/nar/7.4.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zipser D., Lipsich L., Kwoh J. Mapping functional domains in the promoter region of the herpes thymidine kinase gene. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6276–6280. doi: 10.1073/pnas.78.10.6276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Villiers J., Schaffner W. A small segment of polyoma virus DNA enhances the expression of a cloned beta-globin gene over a distance of 1400 base pairs. Nucleic Acids Res. 1981 Dec 11;9(23):6251–6264. doi: 10.1093/nar/9.23.6251. [DOI] [PMC free article] [PubMed] [Google Scholar]