Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1997 Oct;71(10):8056–8060. doi: 10.1128/jvi.71.10.8056-8060.1997

IE2 protein is insufficient for transcriptional repression of the human cytomegalovirus US3 promoter.

B J Biegalke 1
PMCID: PMC192171  PMID: 9311904

Abstract

Expression of the human cytomegalovirus (HCMV) US3 gene is regulated in part by transcriptional repression mediated through a cis-repressive region located between the TATA box and the transcriptional start site. The US3 cis-repressive element has extensive sequence identity with a similar repressive element in UL122-123 (the major immediate-early gene complex). Repression of UL122-123 is mediated through the interaction of the IE2 protein with cis-repressive sequences. In spite of the similarity of the two repressive elements, IE2 activated rather than repressed transcription from the US3 promoter. Additionally, IE1 or IE1 and IE2 in combination also activated US3 expression. These data demonstrate that regulation of HCMV immediate-early genes is quite complex and involves a number of proteins.

Full Text

The Full Text of this article is available as a PDF (406.0 KB).

Selected References

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

  1. Ahn K., Angulo A., Ghazal P., Peterson P. A., Yang Y., Früh K. Human cytomegalovirus inhibits antigen presentation by a sequential multistep process. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10990–10995. doi: 10.1073/pnas.93.20.10990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biegalke B. J., Geballe A. P. Sequence requirements for activation of the HIV-1 LTR by human cytomegalovirus. Virology. 1991 Jul;183(1):381–385. doi: 10.1016/0042-6822(91)90151-z. [DOI] [PubMed] [Google Scholar]
  3. Biegalke B. J. Regulation of human cytomegalovirus US3 gene transcription by a cis-repressive sequence. J Virol. 1995 Sep;69(9):5362–5367. doi: 10.1128/jvi.69.9.5362-5367.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chan Y. J., Tseng W. P., Hayward G. S. Two distinct upstream regulatory domains containing multicopy cellular transcription factor binding sites provide basal repression and inducible enhancer characteristics to the immediate-early IES (US3) promoter from human cytomegalovirus. J Virol. 1996 Aug;70(8):5312–5328. doi: 10.1128/jvi.70.8.5312-5328.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chee M. S., Bankier A. T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchison C. A., 3rd, Kouzarides T., Martignetti J. A. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol. 1990;154:125–169. doi: 10.1007/978-3-642-74980-3_6. [DOI] [PubMed] [Google Scholar]
  6. Cherrington J. M., Khoury E. L., Mocarski E. S. Human cytomegalovirus ie2 negatively regulates alpha gene expression via a short target sequence near the transcription start site. J Virol. 1991 Feb;65(2):887–896. doi: 10.1128/jvi.65.2.887-896.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Colberg-Poley A. M., Santomenna L. D., Harlow P. P., Benfield P. A., Tenney D. J. Human cytomegalovirus US3 and UL36-38 immediate-early proteins regulate gene expression. J Virol. 1992 Jan;66(1):95–105. doi: 10.1128/jvi.66.1.95-105.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ghazal P., Nelson J. A. Enhancement of RNA polymerase II initiation complexes by a novel DNA control domain downstream from the cap site of the cytomegalovirus major immediate-early promoter. J Virol. 1991 May;65(5):2299–2307. doi: 10.1128/jvi.65.5.2299-2307.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hermiston T. W., Malone C. L., Stinski M. F. Human cytomegalovirus immediate-early two protein region involved in negative regulation of the major immediate-early promoter. J Virol. 1990 Jul;64(7):3532–3536. doi: 10.1128/jvi.64.7.3532-3536.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jones T. R., Muzithras V. P. A cluster of dispensable genes within the human cytomegalovirus genome short component: IRS1, US1 through US5, and the US6 family. J Virol. 1992 Apr;66(4):2541–2546. doi: 10.1128/jvi.66.4.2541-2546.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jones T. R., Sun L. Human cytomegalovirus US2 destabilizes major histocompatibility complex class I heavy chains. J Virol. 1997 Apr;71(4):2970–2979. doi: 10.1128/jvi.71.4.2970-2979.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jones T. R., Wiertz E. J., Sun L., Fish K. N., Nelson J. A., Ploegh H. L. Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11327–11333. doi: 10.1073/pnas.93.21.11327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kollert-Jöns A., Bogner E., Radsak K. A 15-kilobase-pair region of the human cytomegalovirus genome which includes US1 through US13 is dispensable for growth in cell culture. J Virol. 1991 Oct;65(10):5184–5189. doi: 10.1128/jvi.65.10.5184-5189.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lang D., Stamminger T. Minor groove contacts are essential for an interaction of the human cytomegalovirus IE2 protein with its DNA target. Nucleic Acids Res. 1994 Aug 25;22(16):3331–3338. doi: 10.1093/nar/22.16.3331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lang D., Stamminger T. The 86-kilodalton IE-2 protein of human cytomegalovirus is a sequence-specific DNA-binding protein that interacts directly with the negative autoregulatory response element located near the cap site of the IE-1/2 enhancer-promoter. J Virol. 1993 Jan;67(1):323–331. doi: 10.1128/jvi.67.1.323-331.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Liu B., Hermiston T. W., Stinski M. F. A cis-acting element in the major immediate-early (IE) promoter of human cytomegalovirus is required for negative regulation by IE2. J Virol. 1991 Feb;65(2):897–903. doi: 10.1128/jvi.65.2.897-903.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liu B., Stinski M. F. Human cytomegalovirus contains a tegument protein that enhances transcription from promoters with upstream ATF and AP-1 cis-acting elements. J Virol. 1992 Jul;66(7):4434–4444. doi: 10.1128/jvi.66.7.4434-4444.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Macias M. P., Huang L., Lashmit P. E., Stinski M. F. Cellular or viral protein binding to a cytomegalovirus promoter transcription initiation site: effects on transcription. J Virol. 1996 Jun;70(6):3628–3635. doi: 10.1128/jvi.70.6.3628-3635.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Macias M. P., Stinski M. F. An in vitro system for human cytomegalovirus immediate early 2 protein (IE2)-mediated site-dependent repression of transcription and direct binding of IE2 to the major immediate early promoter. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):707–711. doi: 10.1073/pnas.90.2.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pizzorno M. C., Hayward G. S. The IE2 gene products of human cytomegalovirus specifically down-regulate expression from the major immediate-early promoter through a target sequence located near the cap site. J Virol. 1990 Dec;64(12):6154–6165. doi: 10.1128/jvi.64.12.6154-6165.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tenney D. J., Colberg-Poley A. M. Human cytomegalovirus UL36-38 and US3 immediate-early genes: temporally regulated expression of nuclear, cytoplasmic, and polysome-associated transcripts during infection. J Virol. 1991 Dec;65(12):6724–6734. doi: 10.1128/jvi.65.12.6724-6734.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tenney D. J., Santomenna L. D., Goudie K. B., Colberg-Poley A. M. The human cytomegalovirus US3 immediate-early protein lacking the putative transmembrane domain regulates gene expression. Nucleic Acids Res. 1993 Jun 25;21(12):2931–2937. doi: 10.1093/nar/21.12.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Thrower A. R., Bullock G. C., Bissell J. E., Stinski M. F. Regulation of a human cytomegalovirus immediate-early gene (US3) by a silencer-enhancer combination. J Virol. 1996 Jan;70(1):91–100. doi: 10.1128/jvi.70.1.91-100.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Weston K. An enhancer element in the short unique region of human cytomegalovirus regulates the production of a group of abundant immediate early transcripts. Virology. 1988 Feb;162(2):406–416. doi: 10.1016/0042-6822(88)90481-3. [DOI] [PubMed] [Google Scholar]
  25. Winkler M., Stamminger T. A specific subform of the human cytomegalovirus transactivator protein pUL69 is contained within the tegument of virus particles. J Virol. 1996 Dec;70(12):8984–8987. doi: 10.1128/jvi.70.12.8984-8987.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES