Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1996 Apr 1;24(7):1294–1303. doi: 10.1093/nar/24.7.1294

The telobox, a Myb-related telomeric DNA binding motif found in proteins from yeast, plants and human.

T Bilaud 1, C E Koering 1, E Binet-Brasselet 1, K Ancelin 1, A Pollice 1, S M Gasser 1, E Gilson 1
PMCID: PMC145771  PMID: 8614633

Abstract

The yeast TTAGGG binding factor 1 (Tbf1) was identified and cloned through its ability to interact with vertebrate telomeric repeats in vitro. We show here that a sequence of 60 amino acids located in its C-terminus is critical for DNA binding. This sequence exhibits homologies with Myb repeats and is conserved among five proteins from plants, two of which are known to bind telomeric-related sequences, and two proteins from human, including the telomeric repeat binding factor (TRF) and the predicted C-terminal polypeptide, called orf2, from a yet unknown protein. We demonstrate that the 111 C-terminal residues of TRF and the 64 orf2 residues are able to bind the human telomeric repeats specifically. We propose to call the particular Myb-related motif found in these proteins the 'telobox'. Antibodies directed against the Tbf1 telobox detect two proteins in nuclear and mitotic chromosome extracts from human cell lines. Moreover, both proteins bind specifically to telomeric repeats in vitro. TRF is likely to correspond to one of them. Based on their high affinity for the telomeric repeat, we predict that TRF and orf2 play an important role at human telomeres.

Full Text

The Full Text of this article is available as a PDF (203.2 KB).

Selected References

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

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Baranowskij N., Frohberg C., Prat S., Willmitzer L. A novel DNA binding protein with homology to Myb oncoproteins containing only one repeat can function as a transcriptional activator. EMBO J. 1994 Nov 15;13(22):5383–5392. doi: 10.1002/j.1460-2075.1994.tb06873.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Biedenkapp H., Borgmeyer U., Sippel A. E., Klempnauer K. H. Viral myb oncogene encodes a sequence-specific DNA-binding activity. Nature. 1988 Oct 27;335(6193):835–837. doi: 10.1038/335835a0. [DOI] [PubMed] [Google Scholar]
  4. Bouwmeester T., Güehmann S., el-Baradi T., Kalkbrenner F., van Wijk I., Moelling K., Pieler T. Molecular cloning, expression and in vitro functional characterization of Myb-related proteins in Xenopus. Mech Dev. 1992 Mar;37(1-2):57–68. doi: 10.1016/0925-4773(92)90015-c. [DOI] [PubMed] [Google Scholar]
  5. Brigati C., Kurtz S., Balderes D., Vidali G., Shore D. An essential yeast gene encoding a TTAGGG repeat-binding protein. Mol Cell Biol. 1993 Feb;13(2):1306–1314. doi: 10.1128/mcb.13.2.1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cardenas M. E., Bianchi A., de Lange T. A Xenopus egg factor with DNA-binding properties characteristic of terminus-specific telomeric proteins. Genes Dev. 1993 May;7(5):883–894. doi: 10.1101/gad.7.5.883. [DOI] [PubMed] [Google Scholar]
  7. Chikashige Y., Ding D. Q., Funabiki H., Haraguchi T., Mashiko S., Yanagida M., Hiraoka Y. Telomere-led premeiotic chromosome movement in fission yeast. Science. 1994 Apr 8;264(5156):270–273. doi: 10.1126/science.8146661. [DOI] [PubMed] [Google Scholar]
  8. Chong L., van Steensel B., Broccoli D., Erdjument-Bromage H., Hanish J., Tempst P., de Lange T. A human telomeric protein. Science. 1995 Dec 8;270(5242):1663–1667. doi: 10.1126/science.270.5242.1663. [DOI] [PubMed] [Google Scholar]
  9. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ferguson B. M., Fangman W. L. A position effect on the time of replication origin activation in yeast. Cell. 1992 Jan 24;68(2):333–339. doi: 10.1016/0092-8674(92)90474-q. [DOI] [PubMed] [Google Scholar]
  11. Gasser S. M., Laemmli U. K. Improved methods for the isolation of individual and clustered mitotic chromosomes. Exp Cell Res. 1987 Nov;173(1):85–98. doi: 10.1016/0014-4827(87)90334-x. [DOI] [PubMed] [Google Scholar]
  12. Gasser S. M., Laroche T., Falquet J., Boy de la Tour E., Laemmli U. K. Metaphase chromosome structure. Involvement of topoisomerase II. J Mol Biol. 1986 Apr 20;188(4):613–629. doi: 10.1016/s0022-2836(86)80010-9. [DOI] [PubMed] [Google Scholar]
  13. Gilson E., Laroche T., Gasser S. M. Telomeres and the functional architecture of the nucleus. Trends Cell Biol. 1993 Apr;3(4):128–134. doi: 10.1016/0962-8924(93)90175-z. [DOI] [PubMed] [Google Scholar]
  14. Gilson E., Roberge M., Giraldo R., Rhodes D., Gasser S. M. Distortion of the DNA double helix by RAP1 at silencers and multiple telomeric binding sites. J Mol Biol. 1993 May 20;231(2):293–310. doi: 10.1006/jmbi.1993.1283. [DOI] [PubMed] [Google Scholar]
  15. Gottschling D. E., Aparicio O. M., Billington B. L., Zakian V. A. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell. 1990 Nov 16;63(4):751–762. doi: 10.1016/0092-8674(90)90141-z. [DOI] [PubMed] [Google Scholar]
  16. Gottschling D. E., Cech T. R. Chromatin structure of the molecular ends of Oxytricha macronuclear DNA: phased nucleosomes and a telomeric complex. Cell. 1984 Sep;38(2):501–510. doi: 10.1016/0092-8674(84)90505-1. [DOI] [PubMed] [Google Scholar]
  17. Higgins D. G., Bleasby A. J., Fuchs R. CLUSTAL V: improved software for multiple sequence alignment. Comput Appl Biosci. 1992 Apr;8(2):189–191. doi: 10.1093/bioinformatics/8.2.189. [DOI] [PubMed] [Google Scholar]
  18. Ijdo J. W., Wells R. A., Baldini A., Reeders S. T. Improved telomere detection using a telomere repeat probe (TTAGGG)n generated by PCR. Nucleic Acids Res. 1991 Sep 11;19(17):4780–4780. doi: 10.1093/nar/19.17.4780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ishikawa F., Matunis M. J., Dreyfuss G., Cech T. R. Nuclear proteins that bind the pre-mRNA 3' splice site sequence r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n. Mol Cell Biol. 1993 Jul;13(7):4301–4310. doi: 10.1128/mcb.13.7.4301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Larson G. P., Castanotto D., Rossi J. J., Malafa M. P. Isolation and functional analysis of a Kluyveromyces lactis RAP1 homologue. Gene. 1994 Dec 2;150(1):35–41. doi: 10.1016/0378-1119(94)90854-0. [DOI] [PubMed] [Google Scholar]
  21. Lejnine S., Makarov V. L., Langmore J. P. Conserved nucleoprotein structure at the ends of vertebrate and invertebrate chromosomes. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2393–2397. doi: 10.1073/pnas.92.6.2393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lin J. J., Zakian V. A. Isolation and characterization of two Saccharomyces cerevisiae genes that encode proteins that bind to (TG1-3)n single strand telomeric DNA in vitro. Nucleic Acids Res. 1994 Nov 25;22(23):4906–4913. doi: 10.1093/nar/22.23.4906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Liu Z. P., Tye B. K. A yeast protein that binds to vertebrate telomeres and conserved yeast telomeric junctions. Genes Dev. 1991 Jan;5(1):49–59. doi: 10.1101/gad.5.1.49. [DOI] [PubMed] [Google Scholar]
  24. Lombard-Platet G., Jalinot P. Purification by DNA affinity precipitation of the cellular factors HEB1-p67 and HEB1-p94 which bind specifically to the human T-cell leukemia virus type-I 21 bp enhancer. Nucleic Acids Res. 1993 Aug 25;21(17):3935–3942. doi: 10.1093/nar/21.17.3935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Louis E. J., Naumova E. S., Lee A., Naumov G., Haber J. E. The chromosome end in yeast: its mosaic nature and influence on recombinational dynamics. Genetics. 1994 Mar;136(3):789–802. doi: 10.1093/genetics/136.3.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lugert T., Werr W. A novel DNA-binding domain in the Shrunken initiator-binding protein (IBP1). Plant Mol Biol. 1994 Jun;25(3):493–506. doi: 10.1007/BF00043877. [DOI] [PubMed] [Google Scholar]
  27. Martínez-Balbás M. A., Dey A., Rabindran S. K., Ozato K., Wu C. Displacement of sequence-specific transcription factors from mitotic chromatin. Cell. 1995 Oct 6;83(1):29–38. doi: 10.1016/0092-8674(95)90231-7. [DOI] [PubMed] [Google Scholar]
  28. McEachern M. J., Blackburn E. H. A conserved sequence motif within the exceptionally diverse telomeric sequences of budding yeasts. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3453–3457. doi: 10.1073/pnas.91.8.3453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McKay S. J., Cooke H. hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn. Nucleic Acids Res. 1992 Dec 25;20(24):6461–6464. doi: 10.1093/nar/20.24.6461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Miskimins W. K., Roberts M. P., McClelland A., Ruddle F. H. Use of a protein-blotting procedure and a specific DNA probe to identify nuclear proteins that recognize the promoter region of the transferrin receptor gene. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6741–6744. doi: 10.1073/pnas.82.20.6741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nimmo E. R., Cranston G., Allshire R. C. Telomere-associated chromosome breakage in fission yeast results in variegated expression of adjacent genes. EMBO J. 1994 Aug 15;13(16):3801–3811. doi: 10.1002/j.1460-2075.1994.tb06691.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nomura N., Takahashi M., Matsui M., Ishii S., Date T., Sasamoto S., Ishizaki R. Isolation of human cDNA clones of myb-related genes, A-myb and B-myb. Nucleic Acids Res. 1988 Dec 9;16(23):11075–11089. doi: 10.1093/nar/16.23.11075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ogata K., Morikawa S., Nakamura H., Sekikawa A., Inoue T., Kanai H., Sarai A., Ishii S., Nishimura Y. Solution structure of a specific DNA complex of the Myb DNA-binding domain with cooperative recognition helices. Cell. 1994 Nov 18;79(4):639–648. doi: 10.1016/0092-8674(94)90549-5. [DOI] [PubMed] [Google Scholar]
  34. Palladino F., Gasser S. M. Telomere maintenance and gene repression: a common end? Curr Opin Cell Biol. 1994 Jun;6(3):373–379. doi: 10.1016/0955-0674(94)90029-9. [DOI] [PubMed] [Google Scholar]
  35. Palladino F., Laroche T., Gilson E., Axelrod A., Pillus L., Gasser S. M. SIR3 and SIR4 proteins are required for the positioning and integrity of yeast telomeres. Cell. 1993 Nov 5;75(3):543–555. doi: 10.1016/0092-8674(93)90388-7. [DOI] [PubMed] [Google Scholar]
  36. Petracek M. E., Konkel L. M., Kable M. L., Berman J. A Chlamydomonas protein that binds single-stranded G-strand telomere DNA. EMBO J. 1994 Aug 1;13(15):3648–3658. doi: 10.1002/j.1460-2075.1994.tb06672.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Price C. M. Centromeres and telomeres. Curr Opin Cell Biol. 1992 Jun;4(3):379–384. doi: 10.1016/0955-0674(92)90002-t. [DOI] [PubMed] [Google Scholar]
  38. Price C. M. Telomere structure in Euplotes crassus: characterization of DNA-protein interactions and isolation of a telomere-binding protein. Mol Cell Biol. 1990 Jul;10(7):3421–3431. doi: 10.1128/mcb.10.7.3421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Saitou N., Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. doi: 10.1093/oxfordjournals.molbev.a040454. [DOI] [PubMed] [Google Scholar]
  40. Scherthan H., Bähler J., Kohli J. Dynamics of chromosome organization and pairing during meiotic prophase in fission yeast. J Cell Biol. 1994 Oct;127(2):273–285. doi: 10.1083/jcb.127.2.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Slamon D. J., Boone T. C., Murdock D. C., Keith D. E., Press M. F., Larson R. A., Souza L. M. Studies of the human c-myb gene and its product in human acute leukemias. Science. 1986 Jul 18;233(4761):347–351. doi: 10.1126/science.3014652. [DOI] [PubMed] [Google Scholar]
  42. Solano R., Nieto C., Avila J., Cañas L., Diaz I., Paz-Ares J. Dual DNA binding specificity of a petal epidermis-specific MYB transcription factor (MYB.Ph3) from Petunia hybrida. EMBO J. 1995 Apr 18;14(8):1773–1784. doi: 10.1002/j.1460-2075.1995.tb07166.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tommerup H., Dousmanis A., de Lange T. Unusual chromatin in human telomeres. Mol Cell Biol. 1994 Sep;14(9):5777–5785. doi: 10.1128/mcb.14.9.5777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Vourc'h C., Taruscio D., Boyle A. L., Ward D. C. Cell cycle-dependent distribution of telomeres, centromeres, and chromosome-specific subsatellite domains in the interphase nucleus of mouse lymphocytes. Exp Cell Res. 1993 Mar;205(1):142–151. doi: 10.1006/excr.1993.1068. [DOI] [PubMed] [Google Scholar]
  45. Wellinger R. J., Zakian V. A. Lack of positional requirements for autonomously replicating sequence elements on artificial yeast chromosomes. Proc Natl Acad Sci U S A. 1989 Feb;86(3):973–977. doi: 10.1073/pnas.86.3.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wright J. H., Gottschling D. E., Zakian V. A. Saccharomyces telomeres assume a non-nucleosomal chromatin structure. Genes Dev. 1992 Feb;6(2):197–210. doi: 10.1101/gad.6.2.197. [DOI] [PubMed] [Google Scholar]
  47. Zakian V. A. Structure and function of telomeres. Annu Rev Genet. 1989;23:579–604. doi: 10.1146/annurev.ge.23.120189.003051. [DOI] [PubMed] [Google Scholar]
  48. Zervos A. S., Gyuris J., Brent R. Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell. 1993 Jan 29;72(2):223–232. doi: 10.1016/0092-8674(93)90662-a. [DOI] [PubMed] [Google Scholar]
  49. da Costa e Silva O., Klein L., Schmelzer E., Trezzini G. F., Hahlbrock K. BPF-1, a pathogen-induced DNA-binding protein involved in the plant defense response. Plant J. 1993 Jul;4(1):125–135. doi: 10.1046/j.1365-313x.1993.04010125.x. [DOI] [PubMed] [Google Scholar]
  50. de Lange T. Human telomeres are attached to the nuclear matrix. EMBO J. 1992 Feb;11(2):717–724. doi: 10.1002/j.1460-2075.1992.tb05104.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. von Kries J. P., Buhrmester H., Strätling W. H. A matrix/scaffold attachment region binding protein: identification, purification, and mode of binding. Cell. 1991 Jan 11;64(1):123–135. doi: 10.1016/0092-8674(91)90214-j. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES