Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1997 Feb 15;322(Pt 1):155–158. doi: 10.1042/bj3220155

The octamer-binding proteins Oct-1 and Oct-2 repress the HIV long terminal repeat promoter and its transactivation by Tat.

Y Z Liu 1, D S Latchman 1
PMCID: PMC1218171  PMID: 9078256

Abstract

Although the HIV-1 long terminal repeat (LTR) contains four potential binding sites for the octamer-binding protein, Oct-1, which is known to interact with the HIV-1 Tat protein, the effect of the Oct-1 factor on HIV LTR-driven gene expression has not previously been reported. We show here that both Oct-1, and to a lesser extent the related Oct-2 protein, can repress both the basal activity of the HIV-1 LTR and its transactivation by Tat. These effects are still observed with an HIV LTR construct containing only a single octamer-binding site located between the TATA box and the transcriptional start site. The stronger inhibitory effect of Oct-1 on both these promoters is dependent upon its C-terminal region which cannot be effectively replaced by the equivalent region of Oct-2. These effects are discussed in terms of the regulation of HIV LTR activity in different cell types and in response to T-cell activation.

Full Text

The Full Text of this article is available as a PDF (133.7 KB).

Selected References

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

  1. Abken H., Reifenrath B. A procedure to standardize CAT reporter gene assay. Nucleic Acids Res. 1992 Jul 11;20(13):3527–3527. doi: 10.1093/nar/20.13.3527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alonso A., Derse D., Peterlin B. M. Human chromosome 12 is required for optimal interactions between Tat and TAR of human immunodeficiency virus type 1 in rodent cells. J Virol. 1992 Jul;66(7):4617–4621. doi: 10.1128/jvi.66.7.4617-4621.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bagasra O., Khalili K., Seshamma T., Taylor J. P., Pomerantz R. J. TAR-independent replication of human immunodeficiency virus type 1 in glial cells. J Virol. 1992 Dec;66(12):7522–7528. doi: 10.1128/jvi.66.12.7522-7528.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barry P. A., Pratt-Lowe E., Unger R. E., Luciw P. A. Cellular factors regulate transactivation of human immunodeficiency virus type 1. J Virol. 1991 Mar;65(3):1392–1399. doi: 10.1128/jvi.65.3.1392-1399.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berkhout B., Jeang K. T. Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat. J Virol. 1992 Jan;66(1):139–149. doi: 10.1128/jvi.66.1.139-149.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  7. Cullen B. R., Greene W. C. Regulatory pathways governing HIV-1 replication. Cell. 1989 Aug 11;58(3):423–426. doi: 10.1016/0092-8674(89)90420-0. [DOI] [PubMed] [Google Scholar]
  8. Dent C. L., McIndoe G. A., Latchman D. S. The constitutively expressed octamer binding protein OTF-1 and a novel octamer binding protein expressed specifically in cervical cells bind to an octamer-related sequence in the human papillomavirus 16 enhancer. Nucleic Acids Res. 1991 Aug 25;19(16):4531–4535. doi: 10.1093/nar/19.16.4531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dostatni N., Lambert P. F., Sousa R., Ham J., Howley P. M., Yaniv M. The functional BPV-1 E2 trans-activating protein can act as a repressor by preventing formation of the initiation complex. Genes Dev. 1991 Sep;5(9):1657–1671. doi: 10.1101/gad.5.9.1657. [DOI] [PubMed] [Google Scholar]
  10. Gerster T., Balmaceda C. G., Roeder R. G. The cell type-specific octamer transcription factor OTF-2 has two domains required for the activation of transcription. EMBO J. 1990 May;9(5):1635–1643. doi: 10.1002/j.1460-2075.1990.tb08283.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Greenblatt J., Nodwell J. R., Mason S. W. Transcriptional antitermination. Nature. 1993 Jul 29;364(6436):401–406. doi: 10.1038/364401a0. [DOI] [PubMed] [Google Scholar]
  12. Greene W. C. Regulation of HIV-1 gene expression. Annu Rev Immunol. 1990;8:453–475. doi: 10.1146/annurev.iy.08.040190.002321. [DOI] [PubMed] [Google Scholar]
  13. Harrich D., Garcia J., Mitsuyasu R., Gaynor R. TAR independent activation of the human immunodeficiency virus in phorbol ester stimulated T lymphocytes. EMBO J. 1990 Dec;9(13):4417–4423. doi: 10.1002/j.1460-2075.1990.tb07892.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. He X., Treacy M. N., Simmons D. M., Ingraham H. A., Swanson L. W., Rosenfeld M. G. Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature. 1989 Jul 6;340(6228):35–41. doi: 10.1038/340035a0. [DOI] [PubMed] [Google Scholar]
  15. Hoppe-Seyler F., Butz K., zur Hausen H. Repression of the human papillomavirus type 18 enhancer by the cellular transcription factor Oct-1. J Virol. 1991 Oct;65(10):5613–5618. doi: 10.1128/jvi.65.10.5613-5618.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jeang K. T., Chun R., Lin N. H., Gatignol A., Glabe C. G., Fan H. In vitro and in vivo binding of human immunodeficiency virus type 1 Tat protein and Sp1 transcription factor. J Virol. 1993 Oct;67(10):6224–6233. doi: 10.1128/jvi.67.10.6224-6233.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  18. Jones K. A., Peterlin B. M. Control of RNA initiation and elongation at the HIV-1 promoter. Annu Rev Biochem. 1994;63:717–743. doi: 10.1146/annurev.bi.63.070194.003441. [DOI] [PubMed] [Google Scholar]
  19. Jones K. A. Tat and the HIV-1 promoter. Curr Opin Cell Biol. 1993 Jun;5(3):461–468. doi: 10.1016/0955-0674(93)90012-f. [DOI] [PubMed] [Google Scholar]
  20. Kato H., Horikoshi M., Roeder R. G. Repression of HIV-1 transcription by a cellular protein. Science. 1991 Mar 22;251(5000):1476–1479. doi: 10.1126/science.2006421. [DOI] [PubMed] [Google Scholar]
  21. Kaufman J. D., Valandra G., Roderiquez G., Bushar G., Giri C., Norcross M. A. Phorbol ester enhances human immunodeficiency virus-promoted gene expression and acts on a repeated 10-base-pair functional enhancer element. Mol Cell Biol. 1987 Oct;7(10):3759–3766. doi: 10.1128/mcb.7.10.3759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lee G., Wu J., Luu P., Ghazal P., Flores O. Inhibition of the association of RNA polymerase II with the preinitiation complex by a viral transcriptional repressor. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2570–2575. doi: 10.1073/pnas.93.6.2570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lillycrop K. A., Dawson S. J., Estridge J. K., Gerster T., Matthias P., Latchman D. S. Repression of a herpes simplex virus immediate-early promoter by the Oct-2 transcription factor is dependent on an inhibitory region at the N terminus of the protein. Mol Cell Biol. 1994 Nov;14(11):7633–7642. doi: 10.1128/mcb.14.11.7633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lillycrop K. A., Dent C. L., Wheatley S. C., Beech M. N., Ninkina N. N., Wood J. N., Latchman D. S. The octamer-binding protein Oct-2 represses HSV immediate-early genes in cell lines derived from latently infectable sensory neurons. Neuron. 1991 Sep;7(3):381–390. doi: 10.1016/0896-6273(91)90290-g. [DOI] [PubMed] [Google Scholar]
  25. Lillycrop K. A., Latchman D. S. Alternative splicing of the Oct-2 transcription factor RNA is differentially regulated in neuronal cells and B cells and results in protein isoforms with opposite effects on the activity of octamer/TAATGARAT-containing promoters. J Biol Chem. 1992 Dec 15;267(35):24960–24965. [PubMed] [Google Scholar]
  26. Liu Y. Z., Lania L., Latchman D. S. Functional interaction between the HIV-1 Tat transactivator and the inhibitory domain of the Oct-2 cellular transcription factor. AIDS. 1996 Oct;10(12):1323–1329. doi: 10.1097/00002030-199610000-00003. [DOI] [PubMed] [Google Scholar]
  27. Luo Y., Roeder R. G. Cloning, functional characterization, and mechanism of action of the B-cell-specific transcriptional coactivator OCA-B. Mol Cell Biol. 1995 Aug;15(8):4115–4124. doi: 10.1128/mcb.15.8.4115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. MACPHERSON I., STOKER M. Polyoma transformation of hamster cell clones--an investigation of genetic factors affecting cell competence. Virology. 1962 Feb;16:147–151. doi: 10.1016/0042-6822(62)90290-8. [DOI] [PubMed] [Google Scholar]
  29. Morris P. J., Dent C. L., Ring C. J., Latchman D. S. The octamer binding site in the HPV16 regulatory region produces opposite effects on gene expression in cervical and non-cervical cells. Nucleic Acids Res. 1993 Feb 25;21(4):1019–1023. doi: 10.1093/nar/21.4.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Müller-Immerglück M. M., Schaffner W., Matthias P. Transcription factor Oct-2A contains functionally redundant activating domains and works selectively from a promoter but not from a remote enhancer position in non-lymphoid (HeLa) cells. EMBO J. 1990 May;9(5):1625–1634. doi: 10.1002/j.1460-2075.1990.tb08282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  32. O'Hare P., Goding C. R. Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation. Cell. 1988 Feb 12;52(3):435–445. doi: 10.1016/s0092-8674(88)80036-9. [DOI] [PubMed] [Google Scholar]
  33. O'Hare P., Hayward G. S. Comparison of upstream sequence requirements for positive and negative regulation of a herpes simplex virus immediate-early gene by three virus-encoded trans-acting factors. J Virol. 1987 Jan;61(1):190–199. doi: 10.1128/jvi.61.1.190-199.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pengue G., Calabrò V., Bartoli P. C., Pagliuca A., Lania L. Repression of transcriptional activity at a distance by the evolutionarily conserved KRAB domain present in a subfamily of zinc finger proteins. Nucleic Acids Res. 1994 Aug 11;22(15):2908–2914. doi: 10.1093/nar/22.15.2908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  36. Singh H., Sen R., Baltimore D., Sharp P. A. A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes. Nature. 1986 Jan 9;319(6049):154–158. doi: 10.1038/319154a0. [DOI] [PubMed] [Google Scholar]
  37. Staudt L. M., Singh H., Sen R., Wirth T., Sharp P. A., Baltimore D. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature. 1986 Oct 16;323(6089):640–643. doi: 10.1038/323640a0. [DOI] [PubMed] [Google Scholar]
  38. Tanaka M., Lai J. S., Herr W. Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter. Cell. 1992 Feb 21;68(4):755–767. doi: 10.1016/0092-8674(92)90150-b. [DOI] [PubMed] [Google Scholar]
  39. Taylor J. P., Pomerantz R., Bagasra O., Chowdhury M., Rappaport J., Khalili K., Amini S. TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. EMBO J. 1992 Sep;11(9):3395–3403. doi: 10.1002/j.1460-2075.1992.tb05418.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ullman K. S., Flanagan W. M., Edwards C. A., Crabtree G. R. Activation of early gene expression in T lymphocytes by Oct-1 and an inducible protein, OAP40. Science. 1991 Oct 25;254(5031):558–562. doi: 10.1126/science.1683003. [DOI] [PubMed] [Google Scholar]
  41. Wirth T., Priess A., Annweiler A., Zwilling S., Oeler B. Multiple Oct2 isoforms are generated by alternative splicing. Nucleic Acids Res. 1991 Jan 11;19(1):43–51. doi: 10.1093/nar/19.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES