Abstract
The POU domain protein Tst-1/Oct-6 is a transcriptional activator of human papovavirus JC virus in transient transfections. Because of its endogenous expression in myelinating glia, Tst-1/Oct-6 might also be an important determinant for the glia specificity of JC virus in vivo. Activation of viral early and late genes depends on the ability of Tst-1/Oct-6 to interact with an AT-rich element within the viral regulatory region. Here, we show that this element not only is bound by Tst-1/Oct-6 but, in addition, serves as a binding site for the high-mobility-group protein HMG-I/Y. In the presence of HMG-I/Y, Tst-1/Oct-6 exhibited an increased affinity for this AT-rich element. The specificity of this effect was evident from the fact that no stimulation of Tst-1/Oct-6 binding was observed on a site that did not allow binding of HMG-I/Y. In addition, both proteins interacted with each other in solution. Direct contacts were identified between the POU domain of Tst-1/Oct-6 and a short stretch of 10 amino acids in the central portion of HMG-I/Y. These results point to an accessory role for HMG-I/Y in the activation of JC viral gene expression by the POU domain protein Tst-1/Oct-6. In agreement with such a role, HMG-Y synergistically supported the function of Tst-1/Oct-6 in transient transfections, measured on the early promoter of JC virus or on an artificial promoter consisting of only a TATA box and the common binding element for Tst-1 and HMG-I/Y.
Full Text
The Full Text of this article is available as a PDF (482.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bengal E., Ransone L., Scharfmann R., Dwarki V. J., Tapscott S. J., Weintraub H., Verma I. M. Functional antagonism between c-Jun and MyoD proteins: a direct physical association. Cell. 1992 Feb 7;68(3):507–519. doi: 10.1016/0092-8674(92)90187-h. [DOI] [PubMed] [Google Scholar]
- Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chuvpilo S., Schomberg C., Gerwig R., Heinfling A., Reeves R., Grummt F., Serfling E. Multiple closely-linked NFAT/octamer and HMG I(Y) binding sites are part of the interleukin-4 promoter. Nucleic Acids Res. 1993 Dec 11;21(24):5694–5704. doi: 10.1093/nar/21.24.5694. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collarini E. J., Kuhn R., Marshall C. J., Monuki E. S., Lemke G., Richardson W. D. Down-regulation of the POU transcription factor SCIP is an early event in oligodendrocyte differentiation in vitro. Development. 1992 Sep;116(1):193–200. doi: 10.1242/dev.116.1.193. [DOI] [PubMed] [Google Scholar]
- Disney J. E., Johnson K. R., Magnuson N. S., Sylvester S. R., Reeves R. High-mobility group protein HMG-I localizes to G/Q- and C-bands of human and mouse chromosomes. J Cell Biol. 1989 Nov;109(5):1975–1982. doi: 10.1083/jcb.109.5.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Du W., Maniatis T. The high mobility group protein HMG I(Y) can stimulate or inhibit DNA binding of distinct transcription factor ATF-2 isoforms. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11318–11322. doi: 10.1073/pnas.91.24.11318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Du W., Thanos D., Maniatis T. Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements. Cell. 1993 Sep 10;74(5):887–898. doi: 10.1016/0092-8674(93)90468-6. [DOI] [PubMed] [Google Scholar]
- Eckner R., Birnstiel M. L. Cloning of cDNAs coding for human HMG I and HMG Y proteins: both are capable of binding to the octamer sequence motif. Nucleic Acids Res. 1989 Aug 11;17(15):5947–5959. doi: 10.1093/nar/17.15.5947. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fashena S. J., Reeves R., Ruddle N. H. A poly(dA-dT) upstream activating sequence binds high-mobility group I protein and contributes to lymphotoxin (tumor necrosis factor-beta) gene regulation. Mol Cell Biol. 1992 Feb;12(2):894–903. doi: 10.1128/mcb.12.2.894. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Faus I., Hsu H. J., Fuchs E. Oct-6: a regulator of keratinocyte gene expression in stratified squamous epithelia. Mol Cell Biol. 1994 May;14(5):3263–3275. doi: 10.1128/mcb.14.5.3263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frantz G. D., Bohner A. P., Akers R. M., McConnell S. K. Regulation of the POU domain gene SCIP during cerebral cortical development. J Neurosci. 1994 Feb;14(2):472–485. doi: 10.1523/JNEUROSCI.14-02-00472.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frisque R. J., Bream G. L., Cannella M. T. Human polyomavirus JC virus genome. J Virol. 1984 Aug;51(2):458–469. doi: 10.1128/jvi.51.2.458-469.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geierstanger B. H., Volkman B. F., Kremer W., Wemmer D. E. Short peptide fragments derived from HMG-I/Y proteins bind specifically to the minor groove of DNA. Biochemistry. 1994 May 3;33(17):5347–5355. doi: 10.1021/bi00183a043. [DOI] [PubMed] [Google Scholar]
- Hai T., Curran T. Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3720–3724. doi: 10.1073/pnas.88.9.3720. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hara Y., Rovescalli A. C., Kim Y., Nirenberg M. Structure and evolution of four POU domain genes expressed in mouse brain. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3280–3284. doi: 10.1073/pnas.89.8.3280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- He X., Gerrero R., Simmons D. M., Park R. E., Lin C. J., Swanson L. W., Rosenfeld M. G. Tst-1, a member of the POU domain gene family, binds the promoter of the gene encoding the cell surface adhesion molecule P0. Mol Cell Biol. 1991 Mar;11(3):1739–1744. doi: 10.1128/mcb.11.3.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- John S., Reeves R. B., Lin J. X., Child R., Leiden J. M., Thompson C. B., Leonard W. J. Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins. Mol Cell Biol. 1995 Mar;15(3):1786–1796. doi: 10.1128/mcb.15.3.1786. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson K. R., Disney J. E., Wyatt C. R., Reeves R. Expression of mRNAs encoding mammalian chromosomal proteins HMG-I and HMG-Y during cellular proliferation. Exp Cell Res. 1990 Mar;187(1):69–76. doi: 10.1016/0014-4827(90)90118-t. [DOI] [PubMed] [Google Scholar]
- Johnson K. R., Lehn D. A., Elton T. S., Barr P. J., Reeves R. Complete murine cDNA sequence, genomic structure, and tissue expression of the high mobility group protein HMG-I(Y). J Biol Chem. 1988 Dec 5;263(34):18338–18342. [PubMed] [Google Scholar]
- Johnson K. R., Lehn D. A., Reeves R. Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y. Mol Cell Biol. 1989 May;9(5):2114–2123. doi: 10.1128/mcb.9.5.2114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kenney S., Natarajan V., Strike D., Khoury G., Salzman N. P. JC virus enhancer-promoter active in human brain cells. Science. 1984 Dec 14;226(4680):1337–1339. doi: 10.1126/science.6095453. [DOI] [PubMed] [Google Scholar]
- Klemm J. D., Rould M. A., Aurora R., Herr W., Pabo C. O. Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules. Cell. 1994 Apr 8;77(1):21–32. doi: 10.1016/0092-8674(94)90231-3. [DOI] [PubMed] [Google Scholar]
- Kuhn R., Monuki E. S., Lemke G. The gene encoding the transcription factor SCIP has features of an expressed retroposon. Mol Cell Biol. 1991 Sep;11(9):4642–4650. doi: 10.1128/mcb.11.9.4642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lai J. S., Herr W. Ethidium bromide provides a simple tool for identifying genuine DNA-independent protein associations. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958–6962. doi: 10.1073/pnas.89.15.6958. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewis H., Kaszubska W., DeLamarter J. F., Whelan J. Cooperativity between two NF-kappa B complexes, mediated by high-mobility-group protein I(Y), is essential for cytokine-induced expression of the E-selectin promoter. Mol Cell Biol. 1994 Sep;14(9):5701–5709. doi: 10.1128/mcb.14.9.5701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Major E. O., Amemiya K., Tornatore C. S., Houff S. A., Berger J. R. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev. 1992 Jan;5(1):49–73. doi: 10.1128/cmr.5.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meijer D., Graus A., Grosveld G. Mapping the transactivation domain of the Oct-6 POU transcription factor. Nucleic Acids Res. 1992 May 11;20(9):2241–2247. doi: 10.1093/nar/20.9.2241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meijer D., Graus A., Kraay R., Langeveld A., Mulder M. P., Grosveld G. The octamer binding factor Oct6: cDNA cloning and expression in early embryonic cells. Nucleic Acids Res. 1990 Dec 25;18(24):7357–7365. doi: 10.1093/nar/18.24.7357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Monuki E. S., Kuhn R., Lemke G. Cell-specific action and mutable structure of a transcription factor effector domain. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9978–9982. doi: 10.1073/pnas.90.21.9978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Monuki E. S., Kuhn R., Lemke G. Repression of the myelin P0 gene by the POU transcription factor SCIP. Mech Dev. 1993 Jul;42(1-2):15–32. doi: 10.1016/0925-4773(93)90095-f. [DOI] [PubMed] [Google Scholar]
- Monuki E. S., Kuhn R., Weinmaster G., Trapp B. D., Lemke G. Expression and activity of the POU transcription factor SCIP. Science. 1990 Sep 14;249(4974):1300–1303. doi: 10.1126/science.1975954. [DOI] [PubMed] [Google Scholar]
- Monuki E. S., Weinmaster G., Kuhn R., Lemke G. SCIP: a glial POU domain gene regulated by cyclic AMP. Neuron. 1989 Dec;3(6):783–793. doi: 10.1016/0896-6273(89)90247-x. [DOI] [PubMed] [Google Scholar]
- Reeves R., Elton T. S., Nissen M. S., Lehn D., Johnson K. R. Posttranscriptional gene regulation and specific binding of the nonhistone protein HMG-I by the 3' untranslated region of bovine interleukin 2 cDNA. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6531–6535. doi: 10.1073/pnas.84.18.6531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reeves R., Nissen M. S. Interaction of high mobility group-I (Y) nonhistone proteins with nucleosome core particles. J Biol Chem. 1993 Oct 5;268(28):21137–21146. [PubMed] [Google Scholar]
- Reeves R., Nissen M. S. The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. J Biol Chem. 1990 May 25;265(15):8573–8582. [PubMed] [Google Scholar]
- Renner K., Leger H., Wegner M. The POU domain protein Tst-1 and papovaviral large tumor antigen function synergistically to stimulate glia-specific gene expression of JC virus. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6433–6437. doi: 10.1073/pnas.91.14.6433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenfeld M. G. POU-domain transcription factors: pou-er-ful developmental regulators. Genes Dev. 1991 Jun;5(6):897–907. doi: 10.1101/gad.5.6.897. [DOI] [PubMed] [Google Scholar]
- Russnak R. H., Candido E. P., Astell C. R. Interaction of the mouse chromosomal protein HMG-I with the 3' ends of genes in vitro. J Biol Chem. 1988 May 5;263(13):6392–6399. [PubMed] [Google Scholar]
- Schreiber E., Matthias P., Müller M. M., Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. doi: 10.1093/nar/17.15.6419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schöler H. R. Octamania: the POU factors in murine development. Trends Genet. 1991 Oct;7(10):323–329. doi: 10.1016/0168-9525(91)90422-m. [DOI] [PubMed] [Google Scholar]
- Solomon M. J., Strauss F., Varshavsky A. A mammalian high mobility group protein recognizes any stretch of six A.T base pairs in duplex DNA. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1276–1280. doi: 10.1073/pnas.83.5.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strauss F., Varshavsky A. A protein binds to a satellite DNA repeat at three specific sites that would be brought into mutual proximity by DNA folding in the nucleosome. Cell. 1984 Jul;37(3):889–901. doi: 10.1016/0092-8674(84)90424-0. [DOI] [PubMed] [Google Scholar]
- Suzuki N., Rohdewohld H., Neuman T., Gruss P., Schöler H. R. Oct-6: a POU transcription factor expressed in embryonal stem cells and in the developing brain. EMBO J. 1990 Nov;9(11):3723–3732. doi: 10.1002/j.1460-2075.1990.tb07585.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thanos D., Maniatis T. The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell. 1992 Nov 27;71(5):777–789. doi: 10.1016/0092-8674(92)90554-p. [DOI] [PubMed] [Google Scholar]
- Voss J. W., Wilson L., Rosenfeld M. G. POU-domain proteins Pit-1 and Oct-1 interact to form a heteromeric complex and can cooperate to induce expression of the prolactin promoter. Genes Dev. 1991 Jul;5(7):1309–1320. doi: 10.1101/gad.5.7.1309. [DOI] [PubMed] [Google Scholar]
- Wegner M., Drolet D. W., Rosenfeld M. G. POU-domain proteins: structure and function of developmental regulators. Curr Opin Cell Biol. 1993 Jun;5(3):488–498. doi: 10.1016/0955-0674(93)90015-i. [DOI] [PubMed] [Google Scholar]
- Wegner M., Drolet D. W., Rosenfeld M. G. Regulation of JC virus by the POU-domain transcription factor Tst-1: implications for progressive multifocal leukoencephalopathy. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4743–4747. doi: 10.1073/pnas.90.10.4743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wegner M., Zastrow G., Klavinius A., Schwender S., Müller F., Luksza H., Hoppe J., Wienberg J., Grummt F. Cis-acting sequences from mouse rDNA promote plasmid DNA amplification and persistence in mouse cells: implication of HMG-I in their function. Nucleic Acids Res. 1989 Dec 11;17(23):9909–9932. doi: 10.1093/nar/17.23.9909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whitley M. Z., Thanos D., Read M. A., Maniatis T., Collins T. A striking similarity in the organization of the E-selectin and beta interferon gene promoters. Mol Cell Biol. 1994 Oct;14(10):6464–6475. doi: 10.1128/mcb.14.10.6464. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang-Yen H. F., Chambard J. C., Sun Y. L., Smeal T., Schmidt T. J., Drouin J., Karin M. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell. 1990 Sep 21;62(6):1205–1215. doi: 10.1016/0092-8674(90)90396-v. [DOI] [PubMed] [Google Scholar]
- Yang-Yen H. F., Rothblum L. I. Purification and characterization of a high-mobility-group-like DNA-binding protein that stimulates rRNA synthesis in vitro. Mol Cell Biol. 1988 Aug;8(8):3406–3414. doi: 10.1128/mcb.8.8.3406. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhao K., Käs E., Gonzalez E., Laemmli U. K. SAR-dependent mobilization of histone H1 by HMG-I/Y in vitro: HMG-I/Y is enriched in H1-depleted chromatin. EMBO J. 1993 Aug;12(8):3237–3247. doi: 10.1002/j.1460-2075.1993.tb05993.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zwilling S., König H., Wirth T. High mobility group protein 2 functionally interacts with the POU domains of octamer transcription factors. EMBO J. 1995 Mar 15;14(6):1198–1208. doi: 10.1002/j.1460-2075.1995.tb07103.x. [DOI] [PMC free article] [PubMed] [Google Scholar]