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. 1990 Sep;10(9):4996–5001. doi: 10.1128/mcb.10.9.4996

Minimal subenhancer requirements for high-level polyomavirus DNA replication: a cell-specific synergy of PEA3 and PEA1 sites.

R Rochford 1, C T Davis 1, K K Yoshimoto 1, L P Villarreal 1
PMCID: PMC361134  PMID: 2167444

Abstract

The cell-specific regulation of DNA replication has important implications for the molecular strategy of cellular gene control. Mouse polyomavirus (Py) DNA replication is examined as a model of cell-specific replication control. Using an FM3A-derived mouse cell line which expresses early viral proteins (FOP cells), we determined the minimal sequence requirements for viral DNA replication. FOP cells were observed to have much simpler enhancer requirements than 3T6 and many other cells and did not need a B enhancer for high levels of DNA replication. Using these cells, we show that the individual or tandem binding sites for several unrelated trans-acting factors which are generally subfunctional as transcriptional enhancers (simian virus 40 A core, TGTGGAATG; EBP20, TGTGGTTTT; PEA1 [an AP-1 analog], GTGACTAA; PEA2, GACCGCAG; and PEA3, AGGAAG) stimulated low levels of Py DNA replication. The ordered dimeric combination of PEA3 and PEA1 factor-binding sites, however, acted synergistically to stimulate viral DNA replication to high wild-type levels. This is in contrast to prior results in which much larger enhancer sequences were necessary for high-level viral DNA replication. PEA3/PEA1-stimulated DNA replication showed a distance and orientation independence relative to the origin, which disagrees with some but not other prior analyses of enhancer-dependent DNA replication. It therefore appears that trans-acting factor-binding sites (enhansons) can generally activate DNA replication and that the AP-1 family of sites may act synergistically with other associated trans-acting factors to strongly affect Py DNA replication in specific cells.

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Selected References

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  1. Amati P. Polyoma regulatory region: a potential probe for mouse cell differentiation. Cell. 1985 Dec;43(3 Pt 2):561–562. doi: 10.1016/0092-8674(85)90225-9. [DOI] [PubMed] [Google Scholar]
  2. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  3. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  4. Bos T. J., Bohmann D., Tsuchie H., Tjian R., Vogt P. K. v-jun encodes a nuclear protein with enhancer binding properties of AP-1. Cell. 1988 Mar 11;52(5):705–712. doi: 10.1016/0092-8674(88)90408-4. [DOI] [PubMed] [Google Scholar]
  5. Brand A. H., Micklem G., Nasmyth K. A yeast silencer contains sequences that can promote autonomous plasmid replication and transcriptional activation. Cell. 1987 Dec 4;51(5):709–719. doi: 10.1016/0092-8674(87)90094-8. [DOI] [PubMed] [Google Scholar]
  6. Buchman A. R., Kimmerly W. J., Rine J., Kornberg R. D. Two DNA-binding factors recognize specific sequences at silencers, upstream activating sequences, autonomously replicating sequences, and telomeres in Saccharomyces cerevisiae. Mol Cell Biol. 1988 Jan;8(1):210–225. doi: 10.1128/mcb.8.1.210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Campbell B. A., Villarreal L. P. Functional analysis of the individual enhancer core sequences of polyomavirus: cell-specific uncoupling of DNA replication from transcription. Mol Cell Biol. 1988 May;8(5):1993–2004. doi: 10.1128/mcb.8.5.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Campbell B. A., Villarreal L. P. Lymphoid and other tissue-specific phenotypes of polyomavirus enhancer recombinants: positive and negative combinational effects on enhancer specificity and activity. Mol Cell Biol. 1986 Jun;6(6):2068–2079. doi: 10.1128/mcb.6.6.2068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Campbell B. A., Villarreal L. P. Tissue specific phenotypes of polyomavirus A and B enhancer transpositions and duplications: positional and nonpositional effects on replication in lymphoid cells. Virus Genes. 1987 Nov;1(1):23–34. doi: 10.1007/BF00125683. [DOI] [PubMed] [Google Scholar]
  10. Chandrasekharappa S. C., Subramanian K. N. Effects of position and orientation of the 72-base-pair-repeat transcriptional enhancer on replication from the simian virus 40 core origin. J Virol. 1987 Oct;61(10):2973–2980. doi: 10.1128/jvi.61.10.2973-2980.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cheng L., Kelly T. J. Transcriptional activator nuclear factor I stimulates the replication of SV40 minichromosomes in vivo and in vitro. Cell. 1989 Nov 3;59(3):541–551. doi: 10.1016/0092-8674(89)90037-8. [DOI] [PubMed] [Google Scholar]
  12. Chiu R., Boyle W. J., Meek J., Smeal T., Hunter T., Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. doi: 10.1016/0092-8674(88)90076-1. [DOI] [PubMed] [Google Scholar]
  13. Comb M., Mermod N., Hyman S. E., Pearlberg J., Ross M. E., Goodman H. M. Proteins bound at adjacent DNA elements act synergistically to regulate human proenkephalin cAMP inducible transcription. EMBO J. 1988 Dec 1;7(12):3793–3805. doi: 10.1002/j.1460-2075.1988.tb03264.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. DeLucia A. L., Deb S., Partin K., Tegtmeyer P. Functional interactions of the simian virus 40 core origin of replication with flanking regulatory sequences. J Virol. 1986 Jan;57(1):138–144. doi: 10.1128/jvi.57.1.138-144.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. DePamphilis M. L. Transcriptional elements as components of eukaryotic origins of DNA replication. Cell. 1988 Mar 11;52(5):635–638. doi: 10.1016/0092-8674(88)90398-4. [DOI] [PubMed] [Google Scholar]
  16. Del Vecchio A. M., Steinman R. A., Ricciardi R. P. An element of the BK virus enhancer required for DNA replication. J Virol. 1989 Apr;63(4):1514–1524. doi: 10.1128/jvi.63.4.1514-1524.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Delidakis C., Kafatos F. C. Amplification of a chorion gene cluster in Drosophila is subject to multiple cis-regulatory elements and to long-range position effects. J Mol Biol. 1987 Sep 5;197(1):11–26. doi: 10.1016/0022-2836(87)90605-x. [DOI] [PubMed] [Google Scholar]
  18. Engel D. A., Hardy S., Shenk T. cAMP acts in synergy with E1A protein to activate transcription of the adenovirus early genes E4 and E1A. Genes Dev. 1988 Dec;2(12A):1517–1528. doi: 10.1101/gad.2.12a.1517. [DOI] [PubMed] [Google Scholar]
  19. Enver T., Brewer A. C., Patient R. K. Role for DNA replication in beta-globin gene activation. Mol Cell Biol. 1988 Mar;8(3):1301–1308. doi: 10.1128/mcb.8.3.1301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Falaschi A., Biamonti G., Cobianchi F., Csordas-Toth E., Faulkner G., Giacca M., Pedacchia D., Perini G., Riva S., Tribioli C. Presence of transcription signals in two putative DNA replication origins of human cells. Biochim Biophys Acta. 1988 Dec 20;951(2-3):430–442. doi: 10.1016/0167-4781(88)90117-0. [DOI] [PubMed] [Google Scholar]
  21. Franza B. R., Jr, Rauscher F. J., 3rd, Josephs S. F., Curran T. The Fos complex and Fos-related antigens recognize sequence elements that contain AP-1 binding sites. Science. 1988 Mar 4;239(4844):1150–1153. doi: 10.1126/science.2964084. [DOI] [PubMed] [Google Scholar]
  22. Hai T. W., Liu F., Allegretto E. A., Karin M., Green M. R. A family of immunologically related transcription factors that includes multiple forms of ATF and AP-1. Genes Dev. 1988 Oct;2(10):1216–1226. doi: 10.1101/gad.2.10.1216. [DOI] [PubMed] [Google Scholar]
  23. Halazonetis T. D., Georgopoulos K., Greenberg M. E., Leder P. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell. 1988 Dec 2;55(5):917–924. doi: 10.1016/0092-8674(88)90147-x. [DOI] [PubMed] [Google Scholar]
  24. Hammerschmidt W., Sugden B. Identification and characterization of oriLyt, a lytic origin of DNA replication of Epstein-Barr virus. Cell. 1988 Nov 4;55(3):427–433. doi: 10.1016/0092-8674(88)90028-1. [DOI] [PubMed] [Google Scholar]
  25. Hatton K. S., Dhar V., Brown E. H., Iqbal M. A., Stuart S., Didamo V. T., Schildkraut C. L. Replication program of active and inactive multigene families in mammalian cells. Mol Cell Biol. 1988 May;8(5):2149–2158. doi: 10.1128/mcb.8.5.2149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hearing P., Shenk T. The adenovirus type 5 E1A transcriptional control region contains a duplicated enhancer element. Cell. 1983 Jul;33(3):695–703. doi: 10.1016/0092-8674(83)90012-0. [DOI] [PubMed] [Google Scholar]
  27. Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
  28. Iguchi-Ariga S. M., Okazaki T., Itani T., Ogata M., Sato Y., Ariga H. An initiation site of DNA replication with transcriptional enhancer activity present upstream of the c-myc gene. EMBO J. 1988 Oct;7(10):3135–3142. doi: 10.1002/j.1460-2075.1988.tb03180.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Imler J. L., Schatz C., Wasylyk C., Chatton B., Wasylyk B. A Harvey-ras responsive transcription element is also responsive to a tumour-promoter and to serum. Nature. 1988 Mar 17;332(6161):275–278. doi: 10.1038/332275a0. [DOI] [PubMed] [Google Scholar]
  30. Johnson P. F., Landschulz W. H., Graves B. J., McKnight S. L. Identification of a rat liver nuclear protein that binds to the enhancer core element of three animal viruses. Genes Dev. 1987 Apr;1(2):133–146. doi: 10.1101/gad.1.2.133. [DOI] [PubMed] [Google Scholar]
  31. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  32. Kerr L. D., Holt J. T., Matrisian L. M. Growth factors regulate transin gene expression by c-fos-dependent and c-fos-independent pathways. Science. 1988 Dec 9;242(4884):1424–1427. doi: 10.1126/science.2462278. [DOI] [PubMed] [Google Scholar]
  33. Kryszke M. H., Piette J., Yaniv M. Induction of a factor that binds to the polyoma virus A enhancer on differentiation of embryonal carcinoma cells. Nature. 1987 Jul 16;328(6127):254–256. doi: 10.1038/328254a0. [DOI] [PubMed] [Google Scholar]
  34. Kumar R., Yoon K. P., Subramanian K. N. Replication from a proximal simian virus 40 origin is severely inhibited by multiple reiterations of the 72-base-pair repeat enhancer sequence. Mol Cell Biol. 1988 Apr;8(4):1509–1517. doi: 10.1128/mcb.8.4.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lamph W. W., Wamsley P., Sassone-Corsi P., Verma I. M. Induction of proto-oncogene JUN/AP-1 by serum and TPA. Nature. 1988 Aug 18;334(6183):629–631. doi: 10.1038/334629a0. [DOI] [PubMed] [Google Scholar]
  36. Lee W., Haslinger A., Karin M., Tjian R. Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature. 1987 Jan 22;325(6102):368–372. doi: 10.1038/325368a0. [DOI] [PubMed] [Google Scholar]
  37. Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
  38. Lusky M., Botchan M. R. A bovine papillomavirus type 1-encoded modulator function is dispensable for transient viral replication but is required for establishment of the stable plasmid state. J Virol. 1986 Nov;60(2):729–742. doi: 10.1128/jvi.60.2.729-742.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Martin M. E., Piette J., Yaniv M., Tang W. J., Folk W. R. Activation of the polyomavirus enhancer by a murine activator protein 1 (AP1) homolog and two contiguous proteins. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5839–5843. doi: 10.1073/pnas.85.16.5839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Mermod N., Williams T. J., Tjian R. Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro. Nature. 1988 Apr 7;332(6164):557–561. doi: 10.1038/332557a0. [DOI] [PubMed] [Google Scholar]
  41. Mueller C. R., Muller W. J., Hassell J. A. The polyomavirus enhancer comprises multiple functional elements. J Virol. 1988 May;62(5):1667–1678. doi: 10.1128/jvi.62.5.1667-1678.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Muller W. J., Dufort D., Hassell J. A. Multiple subelements within the polyomavirus enhancer function synergistically to activate DNA replication. Mol Cell Biol. 1988 Nov;8(11):5000–5015. doi: 10.1128/mcb.8.11.5000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. O'Connor D. T., Subramani S. Do transcriptional enhancers also augment DNA replication? Nucleic Acids Res. 1988 Dec 9;16(23):11207–11222. doi: 10.1093/nar/16.23.11207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Piette J., Hirai S., Yaniv M. Constitutive synthesis of activator protein 1 transcription factor after viral transformation of mouse fibroblasts. Proc Natl Acad Sci U S A. 1988 May;85(10):3401–3405. doi: 10.1073/pnas.85.10.3401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Piette J., Yaniv M. Molecular analysis of the interaction between an enhancer binding factor and its DNA target. Nucleic Acids Res. 1986 Dec 22;14(24):9595–9611. doi: 10.1093/nar/14.24.9595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Piette J., Yaniv M. Two different factors bind to the alpha-domain of the polyoma virus enhancer, one of which also interacts with the SV40 and c-fos enhancers. EMBO J. 1987 May;6(5):1331–1337. doi: 10.1002/j.1460-2075.1987.tb02372.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Prives C., Murakami Y., Kern F. G., Folk W., Basilico C., Hurwitz J. DNA sequence requirements for replication of polyomavirus DNA in vivo and in vitro. Mol Cell Biol. 1987 Oct;7(10):3694–3704. doi: 10.1128/mcb.7.10.3694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Pruijn G. J., van Driel W., van Miltenburg R. T., van der Vliet P. C. Promoter and enhancer elements containing a conserved sequence motif are recognized by nuclear factor III, a protein stimulating adenovirus DNA replication. EMBO J. 1987 Dec 1;6(12):3771–3778. doi: 10.1002/j.1460-2075.1987.tb02712.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Rauscher F. J., 3rd, Cohen D. R., Curran T., Bos T. J., Vogt P. K., Bohmann D., Tjian R., Franza B. R., Jr Fos-associated protein p39 is the product of the jun proto-oncogene. Science. 1988 May 20;240(4855):1010–1016. doi: 10.1126/science.3130660. [DOI] [PubMed] [Google Scholar]
  50. Rochford R., Campbell B. A., Villarreal L. P. Genetic analysis of the enhancer requirements for polyomavirus DNA replication in mice. J Virol. 1990 Feb;64(2):476–485. doi: 10.1128/jvi.64.2.476-485.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Ryseck R. P., Hirai S. I., Yaniv M., Bravo R. Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts. Nature. 1988 Aug 11;334(6182):535–537. doi: 10.1038/334535a0. [DOI] [PubMed] [Google Scholar]
  52. Shepard A., Clarke J., Herr W. Simian virus 40 revertant enhancers exhibit restricted host ranges for enhancer function. J Virol. 1988 Sep;62(9):3364–3370. doi: 10.1128/jvi.62.9.3364-3370.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Spradling A. C., de Cicco D. V., Wakimoto B. T., Levine J. F., Kalfayan L. J., Cooley L. Amplification of the X-linked Drosophila chorion gene cluster requires a region upstream from the s38 chorion gene. EMBO J. 1987 Apr;6(4):1045–1053. doi: 10.1002/j.1460-2075.1987.tb04857.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Svetlova M. P., Perelygina L. M., Dube Sh, Tomilin N. V. Ochistka iz iadernoi fraktsii kletok HeLa i nekotorye svoistva belka, sviazyvaiushchego klonirovannyi fragment satellitnoi DNK III cheloveka. Mol Gen Mikrobiol Virusol. 1988 Apr;(4):19–22. [PubMed] [Google Scholar]
  55. Turner R., Tjian R. Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cFos-cJun heterodimers. Science. 1989 Mar 31;243(4899):1689–1694. doi: 10.1126/science.2494701. [DOI] [PubMed] [Google Scholar]
  56. Veldman G. M., Lupton S., Kamen R. Polyomavirus enhancer contains multiple redundant sequence elements that activate both DNA replication and gene expression. Mol Cell Biol. 1985 Apr;5(4):649–658. doi: 10.1128/mcb.5.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Wasylyk B., Imler J. L., Chatton B., Schatz C., Wasylyk C. Negative and positive factors determine the activity of the polyoma virus enhancer alpha domain in undifferentiated and differentiated cell types. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7952–7956. doi: 10.1073/pnas.85.21.7952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Wasylyk C., Flores P., Gutman A., Wasylyk B. PEA3 is a nuclear target for transcription activation by non-nuclear oncogenes. EMBO J. 1989 Nov;8(11):3371–3378. doi: 10.1002/j.1460-2075.1989.tb08500.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Wasylyk C., Imler J. L., Perez-Mutul J., Wasylyk B. The c-Ha-ras oncogene and a tumor promoter activate the polyoma virus enhancer. Cell. 1987 Feb 13;48(3):525–534. doi: 10.1016/0092-8674(87)90203-0. [DOI] [PubMed] [Google Scholar]
  60. Wasylyk C., Imler J. L., Wasylyk B. Transforming but not immortalizing oncogenes activate the transcription factor PEA1. EMBO J. 1988 Aug;7(8):2475–2483. doi: 10.1002/j.1460-2075.1988.tb03094.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Yamaguchi Y., Satake M., Ito Y. Two overlapping sequence motifs within the polyomavirus enhancer are independently the targets of stimulation by both the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the Ha-ras oncogene. J Virol. 1989 Mar;63(3):1040–1048. doi: 10.1128/jvi.63.3.1040-1048.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. de Villiers J., Schaffner W., Tyndall C., Lupton S., Kamen R. Polyoma virus DNA replication requires an enhancer. Nature. 1984 Nov 15;312(5991):242–246. doi: 10.1038/312242a0. [DOI] [PubMed] [Google Scholar]

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