Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1991 Nov;65(11):6084–6093. doi: 10.1128/jvi.65.11.6084-6093.1991

Helix-loop-helix transcriptional activators bind to a sequence in glucocorticoid response elements of retrovirus enhancers.

B Corneliussen 1, A Thornell 1, B Hallberg 1, T Grundström 1
PMCID: PMC250283  PMID: 1681116

Abstract

A family of nuclear proteins, designated SL3-3 enhancer factors 2 (SEF2), were found to interact with an Ephrussi box-like motif within the glucocorticoid response element in the enhancer of the murine leukemia virus SL3-3. Mutation of the DNA sequence decreased the basal enhancer activity in various cell lines. The important nucleotides for binding of SEF2 are conserved in most type C retroviruses. Various cell types displayed differences both in the sets of SEF2-DNA complexes formed and in their amounts. A cDNA which encoded a protein that interacted specifically with the SEF2-binding sequence was isolated from human thymocytes. The nucleotide sequence specificity of the recombinant protein, expressed in Escherichia coli, corresponded to that of at least one of the nuclear SEF2 proteins. Sequence analysis of the cDNA revealed that it belongs to the basic helix-loop-helix class of DNA-binding proteins. Several mRNA transcripts of different sizes were identified. Molecular analysis of cDNA clones revealed multiple related mRNA species containing alternative coding regions, which are most probably a result of differential splicing.

Full text

PDF

Images in this article

6086Image
on p.6086
6088Image
on p.6088
6088Image
on p.6088
6089Image
on p.6089

Selected References

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

  1. Ariga H., Imamura Y., Iguchi-Ariga S. M. DNA replication origin and transcriptional enhancer in c-myc gene share the c-myc protein binding sequences. EMBO J. 1989 Dec 20;8(13):4273–4279. doi: 10.1002/j.1460-2075.1989.tb08613.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker P. E., Gillis S., Smith K. A. Monoclonal cytolytic T-cell lines. J Exp Med. 1979 Jan 1;149(1):273–278. doi: 10.1084/jem.149.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Caudy M., Vässin H., Brand M., Tuma R., Jan L. Y., Jan Y. N. daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex. Cell. 1988 Dec 23;55(6):1061–1067. doi: 10.1016/0092-8674(88)90250-4. [DOI] [PubMed] [Google Scholar]
  4. Celander D., Haseltine W. A. Glucocorticoid regulation of murine leukemia virus transcription elements is specified by determinants within the viral enhancer region. J Virol. 1987 Feb;61(2):269–275. doi: 10.1128/jvi.61.2.269-275.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Celander D., Haseltine W. A. Tissue-specific transcription preference as a determinant of cell tropism and leukaemogenic potential of murine retroviruses. Nature. 1984 Nov 8;312(5990):159–162. doi: 10.1038/312159a0. [DOI] [PubMed] [Google Scholar]
  6. Celander D., Hsu B. L., Haseltine W. A. Regulatory elements within the murine leukemia virus enhancer regions mediate glucocorticoid responsiveness. J Virol. 1988 Apr;62(4):1314–1322. doi: 10.1128/jvi.62.4.1314-1322.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen Q., Cheng J. T., Tasi L. H., Schneider N., Buchanan G., Carroll A., Crist W., Ozanne B., Siciliano M. J., Baer R. The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein. EMBO J. 1990 Feb;9(2):415–424. doi: 10.1002/j.1460-2075.1990.tb08126.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
  9. Ephrussi A., Church G. M., Tonegawa S., Gilbert W. B lineage--specific interactions of an immunoglobulin enhancer with cellular factors in vivo. Science. 1985 Jan 11;227(4683):134–140. doi: 10.1126/science.3917574. [DOI] [PubMed] [Google Scholar]
  10. GORER P. A. Studies in antibody response of mice to tumour inoculation. Br J Cancer. 1950 Dec;4(4):372–379. doi: 10.1038/bjc.1950.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Golemis E. A., Speck N. A., Hopkins N. Alignment of U3 region sequences of mammalian type C viruses: identification of highly conserved motifs and implications for enhancer design. J Virol. 1990 Feb;64(2):534–542. doi: 10.1128/jvi.64.2.534-542.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hallberg B., Grundström T. Tissue specific sequence motifs in the enhancer of the leukaemogenic mouse retrovirus SL3-3. Nucleic Acids Res. 1988 Jul 11;16(13):5927–5944. doi: 10.1093/nar/16.13.5927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  14. Henthorn P., Kiledjian M., Kadesch T. Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. Science. 1990 Jan 26;247(4941):467–470. doi: 10.1126/science.2105528. [DOI] [PubMed] [Google Scholar]
  15. Jantzen H. M., Strähle U., Gloss B., Stewart F., Schmid W., Boshart M., Miksicek R., Schütz G. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell. 1987 Apr 10;49(1):29–38. doi: 10.1016/0092-8674(87)90752-5. [DOI] [PubMed] [Google Scholar]
  16. Jones N. C., Rigby P. W., Ziff E. B. Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses. Genes Dev. 1988 Mar;2(3):267–281. doi: 10.1101/gad.2.3.267. [DOI] [PubMed] [Google Scholar]
  17. Kearney J. F., Radbruch A., Liesegang B., Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [PubMed] [Google Scholar]
  18. Kim K. J., Weinbaum F. I., Mathieson B. J., McKeever P. E., Asofsky R. Characteristics of BALB/C T cell lymphomas grown as continuous in vitro lines. J Immunol. 1978 Jul;121(1):339–344. [PubMed] [Google Scholar]
  19. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  20. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  21. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  22. Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
  23. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  24. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  25. Mellentin J. D., Murre C., Donlon T. A., McCaw P. S., Smith S. D., Carroll A. J., McDonald M. E., Baltimore D., Cleary M. L. The gene for enhancer binding proteins E12/E47 lies at the t(1;19) breakpoint in acute leukemias. Science. 1989 Oct 20;246(4928):379–382. doi: 10.1126/science.2799390. [DOI] [PubMed] [Google Scholar]
  26. Mellentin J. D., Smith S. D., Cleary M. L. lyl-1, a novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix-loop-helix DNA binding motif. Cell. 1989 Jul 14;58(1):77–83. doi: 10.1016/0092-8674(89)90404-2. [DOI] [PubMed] [Google Scholar]
  27. Meselson M., Yuan R. DNA restriction enzyme from E. coli. Nature. 1968 Mar 23;217(5134):1110–1114. doi: 10.1038/2171110a0. [DOI] [PubMed] [Google Scholar]
  28. Messing J., Crea R., Seeburg P. H. A system for shotgun DNA sequencing. Nucleic Acids Res. 1981 Jan 24;9(2):309–321. doi: 10.1093/nar/9.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mohit B., Fan K. Hybrid cell line from a cloned immunoglobulin-producing mouse myeloma and a nonproducing mouse lymphoma. Science. 1971 Jan 8;171(3966):75–77. doi: 10.1126/science.171.3966.75. [DOI] [PubMed] [Google Scholar]
  30. Moss L. G., Moss J. B., Rutter W. J. Systematic binding analysis of the insulin gene transcription control region: insulin and immunoglobulin enhancers utilize similar transactivators. Mol Cell Biol. 1988 Jun;8(6):2620–2627. doi: 10.1128/mcb.8.6.2620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
  33. Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. doi: 10.1016/0092-8674(89)90434-0. [DOI] [PubMed] [Google Scholar]
  34. Nilsson P., Hallberg B., Thornell A., Grundström T. Mutant analysis of protein interactions with a nuclear factor I binding site in the SL3-3 virus enhancer. Nucleic Acids Res. 1989 Jun 12;17(11):4061–4075. doi: 10.1093/nar/17.11.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
  36. Oi V. T., Morrison S. L., Herzenberg L. A., Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. doi: 10.1073/pnas.80.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pedersen F. S., Crowther R. L., Tenney D. Y., Reimold A. M., Haseltine W. A. Novel leukaemogenic retroviruses isolated from cell line derived from spontaneous AKR tumour. Nature. 1981 Jul 9;292(5819):167–170. doi: 10.1038/292167a0. [DOI] [PubMed] [Google Scholar]
  38. Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. doi: 10.1038/335683a0. [DOI] [PubMed] [Google Scholar]
  39. Rushlow C. A., Hogan A., Pinchin S. M., Howe K. M., Lardelli M., Ish-Horowicz D. The Drosophila hairy protein acts in both segmentation and bristle patterning and shows homology to N-myc. EMBO J. 1989 Oct;8(10):3095–3103. doi: 10.1002/j.1460-2075.1989.tb08461.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Singh H., LeBowitz J. H., Baldwin A. S., Jr, Sharp P. A. Molecular cloning of an enhancer binding protein: isolation by screening of an expression library with a recognition site DNA. Cell. 1988 Feb 12;52(3):415–423. doi: 10.1016/s0092-8674(88)80034-5. [DOI] [PubMed] [Google Scholar]
  41. Speck N. A., Renjifo B., Golemis E., Fredrickson T. N., Hartley J. W., Hopkins N. Mutation of the core or adjacent LVb elements of the Moloney murine leukemia virus enhancer alters disease specificity. Genes Dev. 1990 Feb;4(2):233–242. doi: 10.1101/gad.4.2.233. [DOI] [PubMed] [Google Scholar]
  42. Speck N. A., Renjifo B., Hopkins N. Point mutations in the Moloney murine leukemia virus enhancer identify a lymphoid-specific viral core motif and 1,3-phorbol myristate acetate-inducible element. J Virol. 1990 Feb;64(2):543–550. doi: 10.1128/jvi.64.2.543-550.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Thisse B., Stoetzel C., Gorostiza-Thisse C., Perrin-Schmitt F. Sequence of the twist gene and nuclear localization of its protein in endomesodermal cells of early Drosophila embryos. EMBO J. 1988 Jul;7(7):2175–2183. doi: 10.1002/j.1460-2075.1988.tb03056.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Thornell A., Hallberg B., Grundström T. Differential protein binding in lymphocytes to a sequence in the enhancer of the mouse retrovirus SL3-3. Mol Cell Biol. 1988 Apr;8(4):1625–1637. doi: 10.1128/mcb.8.4.1625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Villares R., Cabrera C. V. The achaete-scute gene complex of D. melanogaster: conserved domains in a subset of genes required for neurogenesis and their homology to myc. Cell. 1987 Jul 31;50(3):415–424. doi: 10.1016/0092-8674(87)90495-8. [DOI] [PubMed] [Google Scholar]
  47. Vinson C. R., LaMarco K. L., Johnson P. F., Landschulz W. H., McKnight S. L. In situ detection of sequence-specific DNA binding activity specified by a recombinant bacteriophage. Genes Dev. 1988 Jul;2(7):801–806. doi: 10.1101/gad.2.7.801. [DOI] [PubMed] [Google Scholar]
  48. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]

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

RESOURCES