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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Oct 29;93(22):12376–12381. doi: 10.1073/pnas.93.22.12376

NF-kappa B homodimer binding within the HIV-1 initiator region and interactions with TFII-I.

M A Montano 1, K Kripke 1, C D Norina 1, P Achacoso 1, L A Herzenberg 1, A L Roy 1, G P Nolan 1
PMCID: PMC37999  PMID: 8901589

Abstract

We show that the binding of Rel p50 and p52 homodimers at sites within the transcriptional initiation region of HIV-1 provides for their ability to interact with other proteins that bind the initiator. The binding of one such protein, the initiator protein TFII-I, to the initiation region of HIV-1 is augmented in the presence of Rel p50 and Rel p52 homodimers. Consistent with this, in vitro Rel homodimers potentiate HIV-1 transcription in a manner dependent upon TFII-I. The findings suggest that Rel dimers may regulate HIV-1 transcription in two ways. First, through binding at the kappa B enhancer sites at (-104 to -80), NF-kappa B p50:p65 participates in classical transcriptional activation. Second, Rel dimers such as p50 or p52 might bind at initiator sequences to regulate the de novo binding of components of certain preinitiation complexes. These findings, and the existence of Rel binding sites at the initiators of other genes, suggest roles for Rel proteins in early events determining transcriptional control.

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Selected References

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  1. Antoni B. A., Rabson A. B., Kinter A., Bodkin M., Poli G. NF-kappa B-dependent and -independent pathways of HIV activation in a chronically infected T cell line. Virology. 1994 Aug 1;202(2):684–694. doi: 10.1006/viro.1994.1390. [DOI] [PubMed] [Google Scholar]
  2. Ballard D. W., Walker W. H., Doerre S., Sista P., Molitor J. A., Dixon E. P., Peffer N. J., Hannink M., Greene W. C. The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function. Cell. 1990 Nov 16;63(4):803–814. doi: 10.1016/0092-8674(90)90146-6. [DOI] [PubMed] [Google Scholar]
  3. Bielinska A., Krasnow S., Nabel G. J. NF-kappa B-mediated activation of the human immunodeficiency virus enhancer: site of transcriptional initiation is independent of the TATA box. J Virol. 1989 Sep;63(9):4097–4100. doi: 10.1128/jvi.63.9.4097-4100.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Du H., Roy A. L., Roeder R. G. Human transcription factor USF stimulates transcription through the initiator elements of the HIV-1 and the Ad-ML promoters. EMBO J. 1993 Feb;12(2):501–511. doi: 10.1002/j.1460-2075.1993.tb05682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fiering S., Northrop J. P., Nolan G. P., Mattila P. S., Crabtree G. R., Herzenberg L. A. Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor. Genes Dev. 1990 Oct;4(10):1823–1834. doi: 10.1101/gad.4.10.1823. [DOI] [PubMed] [Google Scholar]
  6. Fujita T., Nolan G. P., Ghosh S., Baltimore D. Independent modes of transcriptional activation by the p50 and p65 subunits of NF-kappa B. Genes Dev. 1992 May;6(5):775–787. doi: 10.1101/gad.6.5.775. [DOI] [PubMed] [Google Scholar]
  7. Fujita T., Nolan G. P., Liou H. C., Scott M. L., Baltimore D. The candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-kappa B p50 homodimers. Genes Dev. 1993 Jul;7(7B):1354–1363. doi: 10.1101/gad.7.7b.1354. [DOI] [PubMed] [Google Scholar]
  8. Gaynor R. Cellular transcription factors involved in the regulation of HIV-1 gene expression. AIDS. 1992 Apr;6(4):347–363. doi: 10.1097/00002030-199204000-00001. [DOI] [PubMed] [Google Scholar]
  9. Ghosh S., Gifford A. M., Riviere L. R., Tempst P., Nolan G. P., Baltimore D. Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal. Cell. 1990 Sep 7;62(5):1019–1029. doi: 10.1016/0092-8674(90)90276-k. [DOI] [PubMed] [Google Scholar]
  10. Grilli M., Chiu J. J., Lenardo M. J. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol. 1993;143:1–62. doi: 10.1016/s0074-7696(08)61873-2. [DOI] [PubMed] [Google Scholar]
  11. Harrich D., Garcia J., Wu F., Mitsuyasu R., Gonazalez J., Gaynor R. Role of SP1-binding domains in in vivo transcriptional regulation of the human immunodeficiency virus type 1 long terminal repeat. J Virol. 1989 Jun;63(6):2585–2591. doi: 10.1128/jvi.63.6.2585-2591.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henderson A. J., Zou X., Calame K. L. C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/monocytes. J Virol. 1995 Sep;69(9):5337–5344. doi: 10.1128/jvi.69.9.5337-5344.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jain J., Burgeon E., Badalian T. M., Hogan P. G., Rao A. A similar DNA-binding motif in NFAT family proteins and the Rel homology region. J Biol Chem. 1995 Feb 24;270(8):4138–4145. [PubMed] [Google Scholar]
  14. Jones K. A., Luciw P. A., Duchange N. Structural arrangements of transcription control domains within the 5'-untranslated leader regions of the HIV-1 and HIV-2 promoters. Genes Dev. 1988 Sep;2(9):1101–1114. doi: 10.1101/gad.2.9.1101. [DOI] [PubMed] [Google Scholar]
  15. Kato H., Sumimoto H., Pognonec P., Chen C. H., Rosen C. A., Roeder R. G. HIV-1 Tat acts as a processivity factor in vitro in conjunction with cellular elongation factors. Genes Dev. 1992 Apr;6(4):655–666. doi: 10.1101/gad.6.4.655. [DOI] [PubMed] [Google Scholar]
  16. Kretzschmar M., Meisterernst M., Scheidereit C., Li G., Roeder R. G. Transcriptional regulation of the HIV-1 promoter by NF-kappa B in vitro. Genes Dev. 1992 May;6(5):761–774. doi: 10.1101/gad.6.5.761. [DOI] [PubMed] [Google Scholar]
  17. Löchelt M., Muranyi W., Flügel R. M. Human foamy virus genome possesses an internal, Bel-1-dependent and functional promoter. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7317–7321. doi: 10.1073/pnas.90.15.7317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Maciaszek J. W., Talmage D. A., Viglianti G. A. Synergistic activation of simian immunodeficiency virus and human immunodeficiency virus type 1 transcription by retinoic acid and phorbol ester through an NF-kappa B-independent mechanism. J Virol. 1994 Oct;68(10):6598–6604. doi: 10.1128/jvi.68.10.6598-6604.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Manzano-Winkler B., Novina C. D., Roy A. L. TFII is required for transcription of the naturally TATA-less but initiator-containing Vbeta promoter. J Biol Chem. 1996 May 17;271(20):12076–12081. doi: 10.1074/jbc.271.20.12076. [DOI] [PubMed] [Google Scholar]
  20. Margolis D. M., Somasundaran M., Green M. R. Human transcription factor YY1 represses human immunodeficiency virus type 1 transcription and virion production. J Virol. 1994 Feb;68(2):905–910. doi: 10.1128/jvi.68.2.905-910.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Nolan G. P., Ghosh S., Liou H. C., Tempst P., Baltimore D. DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a rel-related polypeptide. Cell. 1991 Mar 8;64(5):961–969. doi: 10.1016/0092-8674(91)90320-x. [DOI] [PubMed] [Google Scholar]
  23. Nolan G. P. NF-AT-AP-1 and Rel-bZIP: hybrid vigor and binding under the influence. Cell. 1994 Jun 17;77(6):795–798. doi: 10.1016/0092-8674(94)90126-0. [DOI] [PubMed] [Google Scholar]
  24. Northrop J. P., Ho S. N., Chen L., Thomas D. J., Timmerman L. A., Nolan G. P., Admon A., Crabtree G. R. NF-AT components define a family of transcription factors targeted in T-cell activation. Nature. 1994 Jun 9;369(6480):497–502. doi: 10.1038/369497a0. [DOI] [PubMed] [Google Scholar]
  25. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ou S. H., Wu F., Harrich D., García-Martínez L. F., Gaynor R. B. Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. J Virol. 1995 Jun;69(6):3584–3596. doi: 10.1128/jvi.69.6.3584-3596.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pear W. S., Nolan G. P., Scott M. L., Baltimore D. Production of high-titer helper-free retroviruses by transient transfection. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392–8396. doi: 10.1073/pnas.90.18.8392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Perkins N. D., Schmid R. M., Duckett C. S., Leung K., Rice N. R., Nabel G. J. Distinct combinations of NF-kappa B subunits determine the specificity of transcriptional activation. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1529–1533. doi: 10.1073/pnas.89.5.1529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ross E. K., Buckler-White A. J., Rabson A. B., Englund G., Martin M. A. Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types. J Virol. 1991 Aug;65(8):4350–4358. doi: 10.1128/jvi.65.8.4350-4358.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Roy A. L., Malik S., Meisterernst M., Roeder R. G. An alternative pathway for transcription initiation involving TFII-I. Nature. 1993 Sep 23;365(6444):355–359. doi: 10.1038/365355a0. [DOI] [PubMed] [Google Scholar]
  31. Roy A. L., Meisterernst M., Pognonec P., Roeder R. G. Cooperative interaction of an initiator-binding transcription initiation factor and the helix-loop-helix activator USF. Nature. 1991 Nov 21;354(6350):245–248. doi: 10.1038/354245a0. [DOI] [PubMed] [Google Scholar]
  32. Sakaguchi M., Zenzie-Gregory B., Groopman J. E., Smale S. T., Kim S. Y. Alternative pathway for induction of human immunodeficiency virus gene expression: involvement of the general transcription machinery. J Virol. 1991 Oct;65(10):5448–5456. doi: 10.1128/jvi.65.10.5448-5456.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schmid R. M., Perkins N. D., Duckett C. S., Andrews P. C., Nabel G. J. Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65. Nature. 1991 Aug 22;352(6337):733–736. doi: 10.1038/352733a0. [DOI] [PubMed] [Google Scholar]
  34. Seeler J. S., Muchardt C., Suessle A., Gaynor R. B. Transcription factor PRDII-BF1 activates human immunodeficiency virus type 1 gene expression. J Virol. 1994 Feb;68(2):1002–1009. doi: 10.1128/jvi.68.2.1002-1009.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Smale S. T., Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. doi: 10.1016/0092-8674(89)90176-1. [DOI] [PubMed] [Google Scholar]
  36. Tjian R., Maniatis T. Transcriptional activation: a complex puzzle with few easy pieces. Cell. 1994 Apr 8;77(1):5–8. doi: 10.1016/0092-8674(94)90227-5. [DOI] [PubMed] [Google Scholar]
  37. Verrijzer C. P., Chen J. L., Yokomori K., Tjian R. Binding of TAFs to core elements directs promoter selectivity by RNA polymerase II. Cell. 1995 Jun 30;81(7):1115–1125. doi: 10.1016/s0092-8674(05)80016-9. [DOI] [PubMed] [Google Scholar]
  38. Visvanathan K. V., Goodbourn S. Double-stranded RNA activates binding of NF-kappa B to an inducible element in the human beta-interferon promoter. EMBO J. 1989 Apr;8(4):1129–1138. doi: 10.1002/j.1460-2075.1989.tb03483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yoon J. B., Li G., Roeder R. G. Characterization of a family of related cellular transcription factors which can modulate human immunodeficiency virus type 1 transcription in vitro. Mol Cell Biol. 1994 Mar;14(3):1776–1785. doi: 10.1128/mcb.14.3.1776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zenzie-Gregory B., Sheridan P., Jones K. A., Smale S. T. HIV-1 core promoter lacks a simple initiator element but contains a bipartite activator at the transcription start site. J Biol Chem. 1993 Jul 25;268(21):15823–15832. [PubMed] [Google Scholar]

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