Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1995 Sep;15(9):4998–5006. doi: 10.1128/mcb.15.9.4998

Induction of transcription by a viral regulatory protein depends on the relative strengths of functional TATA boxes.

W J Cook 1, B Gu 1, N A DeLuca 1, E B Moynihan 1, D M Coen 1
PMCID: PMC230747  PMID: 7651418

Abstract

The mechanisms by which viral regulatory proteins activate the cellular transcription apparatus without binding to specific DNA elements are not fully understood. Several lines of evidence suggest that activation by one such regulatory protein, herpes simplex virus ICP4, could be mediated, at least in part, by TFIID. To test this model, we replaced the TATA box of the ICP4-responsive viral thymidine kinase gene with functional TATA boxes that displayed different apparent affinities for TATA-box-binding protein as measured by DNase I footprinting. We measured the effects of these TATA boxes on ICP4 induction by constructing ICP4-deficient recombinant viruses containing the different TATA alleles and comparing their expression in cells lacking or expressing ICP4. Overall, ICP4 induced weak TATA boxes (those that displayed low apparent affinity for TATA-box-binding protein and low basal expression) the most (18- to 41-fold) and strong TATA boxes the least (7- to 10-fold). Therefore, ICP4 induction correlated inversely with TATA box strength. Using a reconstituted in vitro transcription assay, we determined that the relative levels of induction by ICP4 of the different TATA alleles were similar to those measured in vivo, suggesting that ICP4 was the only viral protein required for induction. These results fit a model in which ICP4 acts in part to enhance binding of TFIID to the TATA box. We compare and contrast these results with those observed with the viral regulatory proteins adenovirus E1a and simian virus 40 large T antigen and the cellular coactivator PC4.

Full Text

The Full Text of this article is available as a PDF (578.8 KB).

Selected References

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

  1. Aso T., Conaway J. W., Conaway R. C. Role of core promoter structure in assembly of the RNA polymerase II preinitiation complex. A common pathway for formation of preinitiation intermediates at many TATA and TATA-less promoters. J Biol Chem. 1994 Oct 21;269(42):26575–26583. [PubMed] [Google Scholar]
  2. Ballard D. W., Philbrick W. M., Bothwell A. L. Identification of a novel 9-kDa polypeptide from nuclear extracts. DNA binding properties, primary structure, and in vitro expression. J Biol Chem. 1988 Jun 15;263(17):8450–8457. [PubMed] [Google Scholar]
  3. Brady J., Khoury G. trans Activation of the simian virus 40 late transcription unit by T-antigen. Mol Cell Biol. 1985 Jun;5(6):1391–1399. doi: 10.1128/mcb.5.6.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buratowski S., Hahn S., Guarente L., Sharp P. A. Five intermediate complexes in transcription initiation by RNA polymerase II. Cell. 1989 Feb 24;56(4):549–561. doi: 10.1016/0092-8674(89)90578-3. [DOI] [PubMed] [Google Scholar]
  5. Böni J., Coen D. M. Examination of the roles of transcription factor Sp1-binding sites and an octamer motif in trans induction of the herpes simplex virus thymidine kinase gene. J Virol. 1989 Sep;63(9):4088–4092. doi: 10.1128/jvi.63.9.4088-4092.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cai W., Schaffer P. A. Herpes simplex virus type 1 ICP0 regulates expression of immediate-early, early, and late genes in productively infected cells. J Virol. 1992 May;66(5):2904–2915. doi: 10.1128/jvi.66.5.2904-2915.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen J. L., Attardi L. D., Verrijzer C. P., Yokomori K., Tjian R. Assembly of recombinant TFIID reveals differential coactivator requirements for distinct transcriptional activators. Cell. 1994 Oct 7;79(1):93–105. doi: 10.1016/0092-8674(94)90403-0. [DOI] [PubMed] [Google Scholar]
  8. Coen D. M., Weinheimer S. P., McKnight S. L. A genetic approach to promoter recognition during trans induction of viral gene expression. Science. 1986 Oct 3;234(4772):53–59. doi: 10.1126/science.3018926. [DOI] [PubMed] [Google Scholar]
  9. Conaway R. C., Conaway J. W. General initiation factors for RNA polymerase II. Annu Rev Biochem. 1993;62:161–190. doi: 10.1146/annurev.bi.62.070193.001113. [DOI] [PubMed] [Google Scholar]
  10. DeLuca N. A., McCarthy A. M., Schaffer P. A. Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J Virol. 1985 Nov;56(2):558–570. doi: 10.1128/jvi.56.2.558-570.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DeLuca N. A., Schaffer P. A. Activation of immediate-early, early, and late promoters by temperature-sensitive and wild-type forms of herpes simplex virus type 1 protein ICP4. Mol Cell Biol. 1985 Aug;5(8):1997–2008. doi: 10.1128/mcb.5.8.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DeLuca N. A., Schaffer P. A. Activities of herpes simplex virus type 1 (HSV-1) ICP4 genes specifying nonsense peptides. Nucleic Acids Res. 1987 Jun 11;15(11):4491–4511. doi: 10.1093/nar/15.11.4491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. DeLuca N. A., Schaffer P. A. Physical and functional domains of the herpes simplex virus transcriptional regulatory protein ICP4. J Virol. 1988 Mar;62(3):732–743. doi: 10.1128/jvi.62.3.732-743.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Desai P., Ramakrishnan R., Lin Z. W., Osak B., Glorioso J. C., Levine M. The RR1 gene of herpes simplex virus type 1 is uniquely trans activated by ICP0 during infection. J Virol. 1993 Oct;67(10):6125–6135. doi: 10.1128/jvi.67.10.6125-6135.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dixon R. A., Schaffer P. A. Fine-structure mapping and functional analysis of temperature-sensitive mutants in the gene encoding the herpes simplex virus type 1 immediate early protein VP175. J Virol. 1980 Oct;36(1):189–203. doi: 10.1128/jvi.36.1.189-203.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dynlacht B. D., Hoey T., Tjian R. Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. Cell. 1991 Aug 9;66(3):563–576. doi: 10.1016/0092-8674(81)90019-2. [DOI] [PubMed] [Google Scholar]
  17. Everett R. D. A detailed analysis of an HSV-1 early promoter: sequences involved in trans-activation by viral immediate-early gene products are not early-gene specific. Nucleic Acids Res. 1984 Apr 11;12(7):3037–3056. doi: 10.1093/nar/12.7.3037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Faber S. W., Wilcox K. W. Association of the herpes simplex virus regulatory protein ICP4 with specific nucleotide sequences in DNA. Nucleic Acids Res. 1986 Aug 11;14(15):6067–6083. doi: 10.1093/nar/14.15.6067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ferguson B., Krippl B., Andrisani O., Jones N., Westphal H., Rosenberg M. E1A 13S and 12S mRNA products made in Escherichia coli both function as nucleus-localized transcription activators but do not directly bind DNA. Mol Cell Biol. 1985 Oct;5(10):2653–2661. doi: 10.1128/mcb.5.10.2653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Freeman M. J., Powell K. L. DNA-binding properties of a herpes simplex virus immediate early protein. J Virol. 1982 Dec;44(3):1084–1087. doi: 10.1128/jvi.44.3.1084-1087.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gao M., Bouchey J., Curtin K., Knipe D. M. Genetic identification of a portion of the herpes simplex virus ICP8 protein required for DNA-binding. Virology. 1988 Apr;163(2):319–329. doi: 10.1016/0042-6822(88)90272-3. [DOI] [PubMed] [Google Scholar]
  22. Ge H., Roeder R. G. Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes. Cell. 1994 Aug 12;78(3):513–523. doi: 10.1016/0092-8674(94)90428-6. [DOI] [PubMed] [Google Scholar]
  23. Gilinger G., Alwine J. C. Transcriptional activation by simian virus 40 large T antigen: requirements for simple promoter structures containing either TATA or initiator elements with variable upstream factor binding sites. J Virol. 1993 Nov;67(11):6682–6688. doi: 10.1128/jvi.67.11.6682-6688.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Green M. R., Treisman R., Maniatis T. Transcriptional activation of cloned human beta-globin genes by viral immediate-early gene products. Cell. 1983 Nov;35(1):137–148. doi: 10.1016/0092-8674(83)90216-7. [DOI] [PubMed] [Google Scholar]
  25. Gruda M. C., Zabolotny J. M., Xiao J. H., Davidson I., Alwine J. C. Transcriptional activation by simian virus 40 large T antigen: interactions with multiple components of the transcription complex. Mol Cell Biol. 1993 Feb;13(2):961–969. doi: 10.1128/mcb.13.2.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gu B., DeLuca N. Requirements for activation of the herpes simplex virus glycoprotein C promoter in vitro by the viral regulatory protein ICP4. J Virol. 1994 Dec;68(12):7953–7965. doi: 10.1128/jvi.68.12.7953-7965.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Gu B., Rivera-Gonzalez R., Smith C. A., DeLuca N. A. Herpes simplex virus infected cell polypeptide 4 preferentially represses Sp1-activated over basal transcription from its own promoter. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9528–9532. doi: 10.1073/pnas.90.20.9528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hahn S., Buratowski S., Sharp P. A., Guarente L. Yeast TATA-binding protein TFIID binds to TATA elements with both consensus and nonconsensus DNA sequences. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5718–5722. doi: 10.1073/pnas.86.15.5718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Halpern M. E., Smiley J. R. Effects of deletions on expression of the herpes simplex virus thymidine kinase gene from the intact viral genome: the amino terminus of the enzyme is dispensable for catalytic activity. J Virol. 1984 Jun;50(3):733–738. doi: 10.1128/jvi.50.3.733-738.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Holland L. E., Anderson K. P., Shipman C., Jr, Wagner E. K. Viral DNA synthesis is required for the efficient expression of specific herpes simplex virus type 1 mRNA species. Virology. 1980 Feb;101(1):10–24. doi: 10.1016/0042-6822(80)90479-1. [DOI] [PubMed] [Google Scholar]
  31. Hoopes B. C., LeBlanc J. F., Hawley D. K. Kinetic analysis of yeast TFIID-TATA box complex formation suggests a multi-step pathway. J Biol Chem. 1992 Jun 5;267(16):11539–11547. [PubMed] [Google Scholar]
  32. Horikoshi N., Maguire K., Kralli A., Maldonado E., Reinberg D., Weinmann R. Direct interaction between adenovirus E1A protein and the TATA box binding transcription factor IID. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5124–5128. doi: 10.1073/pnas.88.12.5124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Imbalzano A. N., Coen D. M., DeLuca N. A. Herpes simplex virus transactivator ICP4 operationally substitutes for the cellular transcription factor Sp1 for efficient expression of the viral thymidine kinase gene. J Virol. 1991 Feb;65(2):565–574. doi: 10.1128/jvi.65.2.565-574.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Imbalzano A. N., DeLuca N. A. Substitution of a TATA box from a herpes simplex virus late gene in the viral thymidine kinase promoter alters ICP4 inducibility but not temporal expression. J Virol. 1992 Sep;66(9):5453–5463. doi: 10.1128/jvi.66.9.5453-5463.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Imbalzano A. N., Shepard A. A., DeLuca N. A. Functional relevance of specific interactions between herpes simplex virus type 1 ICP4 and sequences from the promoter-regulatory domain of the viral thymidine kinase gene. J Virol. 1990 Jun;64(6):2620–2631. doi: 10.1128/jvi.64.6.2620-2631.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Imbalzano A. N., Zaret K. S., Kingston R. E. Transcription factor (TF) IIB and TFIIA can independently increase the affinity of the TATA-binding protein for DNA. J Biol Chem. 1994 Mar 18;269(11):8280–8286. [PubMed] [Google Scholar]
  37. Irmiere A. F., Manos M. M., Jacobson J. G., Gibbs J. S., Coen D. M. Effect of an amber mutation in the herpes simplex virus thymidine kinase gene on polypeptide synthesis and stability. Virology. 1989 Feb;168(2):210–220. doi: 10.1016/0042-6822(89)90260-2. [DOI] [PubMed] [Google Scholar]
  38. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  39. Keller J. M., Alwine J. C. Analysis of an activatable promoter: sequences in the simian virus 40 late promoter required for T-antigen-mediated trans activation. Mol Cell Biol. 1985 Aug;5(8):1859–1869. doi: 10.1128/mcb.5.8.1859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Kretzschmar M., Kaiser K., Lottspeich F., Meisterernst M. A novel mediator of class II gene transcription with homology to viral immediate-early transcriptional regulators. Cell. 1994 Aug 12;78(3):525–534. doi: 10.1016/0092-8674(94)90429-4. [DOI] [PubMed] [Google Scholar]
  41. Kristie T. M., Roizman B. Alpha 4, the major regulatory protein of herpes simplex virus type 1, is stably and specifically associated with promoter-regulatory domains of alpha genes and of selected other viral genes. Proc Natl Acad Sci U S A. 1986 May;83(10):3218–3222. doi: 10.1073/pnas.83.10.3218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lee W. S., Kao C. C., Bryant G. O., Liu X., Berk A. J. Adenovirus E1A activation domain binds the basic repeat in the TATA box transcription factor. Cell. 1991 Oct 18;67(2):365–376. doi: 10.1016/0092-8674(91)90188-5. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  45. Michael N., Spector D., Mavromara-Nazos P., Kristie T. M., Roizman B. The DNA-binding properties of the major regulatory protein alpha 4 of herpes simplex viruses. Science. 1988 Mar 25;239(4847):1531–1534. doi: 10.1126/science.2832940. [DOI] [PubMed] [Google Scholar]
  46. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  47. Muller M. T. Binding of the herpes simplex virus immediate-early gene product ICP4 to its own transcription start site. J Virol. 1987 Mar;61(3):858–865. doi: 10.1128/jvi.61.3.858-865.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. O'Hare P., Hayward G. S. Evidence for a direct role for both the 175,000- and 110,000-molecular-weight immediate-early proteins of herpes simplex virus in the transactivation of delayed-early promoters. J Virol. 1985 Mar;53(3):751–760. doi: 10.1128/jvi.53.3.751-760.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. Purifoy D. J., Powell K. L. DNA-binding proteins induced by herpes simplex virus type 2 in HEp-2 cells. J Virol. 1976 Aug;19(2):717–731. doi: 10.1128/jvi.19.2.717-731.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Rice P. W., Cole C. N. Efficient transcriptional activation of many simple modular promoters by simian virus 40 large T antigen. J Virol. 1993 Nov;67(11):6689–6697. doi: 10.1128/jvi.67.11.6689-6697.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Rice S. A., Knipe D. M. Gene-specific transactivation by herpes simplex virus type 1 alpha protein ICP27. J Virol. 1988 Oct;62(10):3814–3823. doi: 10.1128/jvi.62.10.3814-3823.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Roeder R. G. The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem Sci. 1991 Nov;16(11):402–408. doi: 10.1016/0968-0004(91)90164-q. [DOI] [PubMed] [Google Scholar]
  54. Schaffer P. A., Bone D. R., Courtney R. J. DNA-negative temperature-sensitive mutants of herpes simplex virus type 1: patterns of viral DNA synthesis after temperature shift-up. J Virol. 1976 Mar;17(3):1043–1048. doi: 10.1128/jvi.17.3.1043-1048.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Sharp J. A., Wagner M. J., Summers W. C. Transcription of herpes simplex virus genes in vivo: overlap of a late promoter with the 3' end of the early thymidine kinase gene. J Virol. 1983 Jan;45(1):10–17. doi: 10.1128/jvi.45.1.10-17.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Simon M. C., Fisch T. M., Benecke B. J., Nevins J. R., Heintz N. Definition of multiple, functionally distinct TATA elements, one of which is a target in the hsp70 promoter for E1A regulation. Cell. 1988 Mar 11;52(5):723–729. doi: 10.1016/0092-8674(88)90410-2. [DOI] [PubMed] [Google Scholar]
  57. Simon M. C., Rooney R. J., Fisch T. M., Heintz N., Nevins J. R. E1A-dependent trans-activation of the c-fos promoter requires the TATAA sequence. Proc Natl Acad Sci U S A. 1990 Jan;87(2):513–517. doi: 10.1073/pnas.87.2.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Smiley J. R., Johnson D. C., Pizer L. I., Everett R. D. The ICP4 binding sites in the herpes simplex virus type 1 glycoprotein D (gD) promoter are not essential for efficient gD transcription during virus infection. J Virol. 1992 Feb;66(2):623–631. doi: 10.1128/jvi.66.2.623-631.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Smith C. A., Bates P., Rivera-Gonzalez R., Gu B., DeLuca N. A. ICP4, the major transcriptional regulatory protein of herpes simplex virus type 1, forms a tripartite complex with TATA-binding protein and TFIIB. J Virol. 1993 Aug;67(8):4676–4687. doi: 10.1128/jvi.67.8.4676-4687.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Taylor I. C., Kingston R. E. E1a transactivation of human HSP70 gene promoter substitution mutants is independent of the composition of upstream and TATA elements. Mol Cell Biol. 1990 Jan;10(1):176–183. doi: 10.1128/mcb.10.1.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Wobbe K. K., Digard P., Staknis D., Coen D. M. Unusual regulation of expression of the herpes simplex virus DNA polymerase gene. J Virol. 1993 Sep;67(9):5419–5425. doi: 10.1128/jvi.67.9.5419-5425.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Wu L., Rosser D. S., Schmidt M. C., Berk A. A TATA box implicated in E1A transcriptional activation of a simple adenovirus 2 promoter. Nature. 1987 Apr 2;326(6112):512–515. doi: 10.1038/326512a0. [DOI] [PubMed] [Google Scholar]
  63. Yeung K. C., Inostroza J. A., Mermelstein F. H., Kannabiran C., Reinberg D. Structure-function analysis of the TBP-binding protein Dr1 reveals a mechanism for repression of class II gene transcription. Genes Dev. 1994 Sep 1;8(17):2097–2109. doi: 10.1101/gad.8.17.2097. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES