Repressor Activator Protein 1 and Its Ligands: Organising Chromatin Domains

  • E. Gilson
  • S. M. Gasser
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC, volume 9)


DNA binding proteins are generally classified as either enzymes, regulatory factors, or structural components of chromatin. The distinction between these groups is not always strict, however, since enzymes (such as DNA topoisomerase II) may also play a structural role in organising chromosomes, and structural proteins (such as histones) can clearly assist in the regulation of gene expression. In the following pages, we review evidence suggesting that the abundant nuclear factor Repressor Activator Protein 1 (RAP1) of budding yeast is both a regulatory factor and a structural element, playing essential roles in both the proper control of gene expression and the maintenance of chromosomal integrity.


Telomere Length Origin Recognition Complex Mating Type Gene Upstream Binding Factor Telomeric Cluster 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Aparicio O, Billington B, Gottschling D (1991) Modifiers of position effect are shared between telomeric and silent mating type loci. Cell 66:1279–1287PubMedCrossRefGoogle Scholar
  2. Bell S, Stillman B (1992) ATP dependent recognition of eukaryotic origins of DNA replication by a multi-protein complex. Nature 7:128–134CrossRefGoogle Scholar
  3. Berman J, Tachibana CY, Tye BK (1986) Identification of a telomere-binding activity from yeast. Proc Natl Acad Sci USA 83:3713–3717PubMedCrossRefGoogle Scholar
  4. Brand AH, Micklem G, Nasmyth K (1987) A yeast silencer countains sequences that can promote autonomous plasmid replication and transcriptional activation. Cell 51:709–719PubMedCrossRefGoogle Scholar
  5. Buchman AR, Lue NF, Kornberg RD (1988) Connections between transcriptional activators, silencers and telomeres as revealed by functional analysis of a yeast DNA-binding protein. Mol Cell Biol 8:5086–5099PubMedGoogle Scholar
  6. Capieaux E, Vignais ML, Sentenac A, Goffeau A (1989) The yeast H+ATPase gene is controlled by promoter binding factor TUF. J Biol Chem 264:7437–7446PubMedGoogle Scholar
  7. Chambers A, Tsang JSH, Stanway C, Kingsman AJ, Kingsman SM (1989) Transcriptional control of the Saccharomyces cerevisiae PGK gene by RAP1. Mol Cell Biol 9:5516–5524PubMedGoogle Scholar
  8. Chambers A, Stanway C, Tsang JSH, Henry Y, Kingsman AJ, Kingsman SM (1990) ARS binding factor 1 binds adjacent to RAP1 at the UASs of the yeast glycolytic genes PGK and PYK1. Nucleic Acids Res 18:5393–5399PubMedCrossRefGoogle Scholar
  9. Cockell M, Palladino F, Laroche T, Kyrion G, Liu C, Lustig A, Gasser SM (1995) The c-termini of SIR4 and RAP1 affect SIR3 localization in yeast: evidence for a multi-component complex required for telomeric silencing. J Cell Biol (in press)Google Scholar
  10. Conrad MN, Wright JH, Wolf AJ, Zakian VA (1990) RAP1 protein interacts with yeast telomeres in vivo: overproduction alters telomere structure and decreases chromosome stability. Cell 63:739–750PubMedCrossRefGoogle Scholar
  11. Devlin C, Tice-Baldwin K, Shore D, Arndt KT (1991) RAP1 is required for BAS1/ BAS2-and GCN4-dependent transcription of the yeast HIS4 gene. Mol Cell Biol 11:3642–3651PubMedGoogle Scholar
  12. Enomoto S, Longtine MS, Berman J (1994) Enhancement of telomere-plasmid segregation by the X-telomere associated sequence in S. cerevisiae involves SIR2, SIR3, SIR4 and ABF1. Genetics 136:757–767PubMedGoogle Scholar
  13. Feldman J, Hicks J, Broach J (1984) Identification of the sites required for repression of a silent mating type locus in yeast. J Mol Biol 178:815–834PubMedCrossRefGoogle Scholar
  14. Gasser SM (1992) Functional aspects of chromosome organization: scaffold attachment regions and their ligands. Adv Mol Cell Biol 4:75–101CrossRefGoogle Scholar
  15. Giesman D, Best L, Tatchell K (1991) The role of RAP1 in the regulation of the MATalpha locus. Mol Cell Biol 11:1069–1079PubMedGoogle Scholar
  16. Gilson E, Roberge M, Giraldo R, Rhodes D, Gasser SM (1993a) Distortion of the DNA double helix by RAP1 at silencers and multiple telomeric binding sites. J Mol Biol 231:293–310PubMedCrossRefGoogle Scholar
  17. Gilson E, Laroche T, Gasser SM (1993b) Telomeres and the functional architecture of the nucleus. Trends Cell Biol 3:128–134PubMedCrossRefGoogle Scholar
  18. Gilson E, Müller T, Sogo J, Laroche T, Gasser SM (1994) RAP1 stimulates singleto double-strand association of yeast telomeric DNA: implications for telomeretelomere interactions. Nucleic Acids Res 22:5310–5320PubMedCrossRefGoogle Scholar
  19. Giraldo R, Rhodes D (1994) The yeast telomere-binding protein RAP1 binds to and promotes the formation of DNA quadruplexes in telomeric DNA. EMBO J 13:2411–2420PubMedGoogle Scholar
  20. Giraldo R, Suzuki M, Chapmen L, Rhodes D (1994) Promotion of parallel DNA quadruplexes by a yeast telomere binding protein: A circular di-chroism study. Proc Natl Acad Sci USA 91:7658–7662PubMedCrossRefGoogle Scholar
  21. Graham IR, Chambers A (1994) Use of a selection technique to identify the diversity of binding sites for the yeast RAP1 transcription factor. Nucleic Acids Res 22:124–130PubMedCrossRefGoogle Scholar
  22. Hardy CFJ, Sussel L, Shore D (1992a) A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation. Genes Dev 6:801–814PubMedCrossRefGoogle Scholar
  23. Hardy CFJ, Balderes D, Shore D (1992b) Dissection of a carboxy-terminal region of the yeast regulatory protein RAP1 with effects on both transcriptional activation and silencing. Mol Cell Biol 12:1209–1217PubMedGoogle Scholar
  24. Hecht A, Laroche T, Strahl-Bolsinger S, Gasser SM, Grunstein M (1995) Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for heterochromatin in yeast. Cell 80 (in press)Google Scholar
  25. Henry YAL, Chambers A, Tsang JSH, Kingsman AJ, Kingsman SM (1990) Characterisation of the DNA binding domain of the yeast RAP1 protein. Nucleic Acids Res 18:2617–2623PubMedCrossRefGoogle Scholar
  26. Hofmann JFX, Laroche T, Brand AH, Gasser SM (1989) RAP-1 factor is necessary for DNA loop formation in vitro at the silent mating type locus HML. Cell 57:725–737PubMedCrossRefGoogle Scholar
  27. Huet J, Cottrelle P, Cool M, Vignais ML, Thiele D, Marck C, Buhler JM, Sentenac A, Fromageot P (1985) A general upstream binding factor for genes of the yeast translational apparatus. EMBO J 4:3547–3559Google Scholar
  28. Kimmerly W, Rine J (1987) Replication and segregation of plasmids containg cisacting regulatory sites of silent mating type genes in S. cerevisiae are controlled by the SIR genes. Mol Cell Biol 7:4225–4237PubMedGoogle Scholar
  29. Kirov N, Zhelnin L, Shah J, Rushlow C (1993) Conversion of a silencer into an enhancer: evidence for a co-repressor in dorsal-mediated repression in Drosophila. EMBO J 12:3193–3199PubMedGoogle Scholar
  30. Klein C, Struhl K (1994) Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity. Mol Cell Biol 14:1920–1928PubMedGoogle Scholar
  31. Klein F, Laroche T, Cardenas ME, Hofmann JFX, Schweizer D, Gasser SM (1992) Localization of RAP1 and topoisomerase II in nuclei and meiotic chromosomes of yeast. J Cell Biol 117:935–948PubMedCrossRefGoogle Scholar
  32. Kramer KM, Haber JE (1994) New telomeres in yeast are initiated with a highly selected subset of TG1-3 repeats. Genes Dev 7:2345–2356CrossRefGoogle Scholar
  33. Kurtz S, Shore D (1991) RAP1 protein activates and silences transcription of mating types genes in yeast. Genes Dev 5:5264–5268CrossRefGoogle Scholar
  34. Kyrion G, Boakye KA, Lustig AJ (1992) C-terminal truncation of RAP1 results in the deregulation of telomere size, stability, and function in Saccharomyces cerevisiae. Mol Cell Biol 12:5159–5173PubMedGoogle Scholar
  35. Kyrion G, Liu K, Lustig AJ (1993) RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. Genes Dev 7:1146–1159PubMedCrossRefGoogle Scholar
  36. Laurenson P, Rine J (1992) Silencers, silencing and heritable transcriptional states. Microbiol Rev 56:543–560PubMedGoogle Scholar
  37. Larson GP, Castanotto D, Rossi JJ, Malafa MP (1994) Isolation and functional analysis of a Kluyveromyces lactis RAP1 homologue. Gene 150:35–41PubMedCrossRefGoogle Scholar
  38. Leroy JL, Guéron M, Mergny JL, Hélène C (1994) Intramolecular folding of a fraquent of the cytosine-rich strand of telomeric DNA into an i-motif. Nucleic Acids Res 22:1600–1606PubMedCrossRefGoogle Scholar
  39. Liu Z, Frantz JD, Gilbert W, Tye BK (1993) Identification and characterization of a nuclease activity specific for G4 tetrastranded DNA. Proc Natl Acad Sci USA 90:3157–3161PubMedCrossRefGoogle Scholar
  40. Liu K, Mao X, Lustig AJ (1994) Mutational analysis defines a C-terminal tail domain of RAP1 essential for telomeric silencing in S. cerevisiae. Genetics 138:1025–1040PubMedGoogle Scholar
  41. Longtine MS, Wilson NM, Petracek ME, Berman J (1989) A yeast telomere binding activity binds to two related telomere sequence motifs and is indistinguishable from RAP1. Curr Genet 16:225–239PubMedCrossRefGoogle Scholar
  42. Longtine MS, Enomoto S, Finstad SL, Berman J (1992) Yeast Telomere repeat Sequences (TRS) improves circular plasmid segregation, and TRS plasmid segregation involves the RAP1 gene product. Mol Cell Biol 12:1997–2009PubMedGoogle Scholar
  43. Lustig AJ (1992) Hoogsteen G-G base pairing is dispensable for telomere healing in yeast. Nucleic Acid Res 20:3021–3028PubMedCrossRefGoogle Scholar
  44. Lustig AJ, Petes TD (1993) Genetic control of simple sequence stability in yeast. In: Davies KE, Warren ST (eds) Genome and analysis: 7: Genome rearrangements and stability. Cold Spring Harbor Laboratories Press, Cold Spring Harbor, NYGoogle Scholar
  45. Lustig AJ, Kurtz S, Shore D (1990) Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length. Science 250:549–553PubMedCrossRefGoogle Scholar
  46. Mahoney DJ, Broach JR (1989) The HML mating-type cassette of Saccharomyces cerevisiae is regulated by two separate but functionally equivalent silencers. Mol Cell Biol 9:4621–4630PubMedGoogle Scholar
  47. McNally FJ, Rine J (1991) A synthetic silencer mediates SIR-dependent functions in saccaromyces cerevisae. Mol Cell Biol 1:5648–5659Google Scholar
  48. Moretti P, Freeman K, Coodly L, Shore D (1994) Evidence that a complex of SIR proteins interacts with the silencer and telomere-binding protein RAP1. Genes Dev 8:2257–2269PubMedCrossRefGoogle Scholar
  49. Müller T, Gilson E, Schmidt R, Giraldo R, Sogo J, Gross H, Gasser SM (1994) Imaging the asymmetric DNA bend induced by Repressor Activator Protein 1 with Scanning Tunneling Microscopy. J Struct Biol 113:1–12PubMedCrossRefGoogle Scholar
  50. Nishizawa M, Suzuki Y, Nogi Y, Matsumoto K, Fukasawa T (1990) Yeast Gal11 protein mediates the transcriptional activation signal of two different transacting factors, Gal4 and general regulatory factor I/repressor/activator site binding protein I/translation upstream factor. Proc Natl Acad Sci USA 87:5373–5377PubMedCrossRefGoogle Scholar
  51. Palladino F, Gasser SM (1994) Telomere maintenance and gene repression: a common end? Curr Opin Cell Biol 6:373–379PubMedCrossRefGoogle Scholar
  52. Palladino F, Laroche T, Gilson E, Axelrod A, Pillus L, Gasser SM (1993) SIR3 and SIR4 proteins are required for the positioning and integrity of yeast telomeres. Cell 75:543–555PubMedCrossRefGoogle Scholar
  53. Planta RJ, Raué HA (1988) Control of ribosome biogenesis in yeast. Trends Genet 4:64–68PubMedCrossRefGoogle Scholar
  54. Porter SE, White MA, Petes TD (1993) Genetic evidence that the meiotic recombination hotspot at the HIS4 locus of Saccharomyces cerevisiae does not represent a site for symmetrically processed double-strand break. Genetics 134:5–19PubMedGoogle Scholar
  55. Renauld H, Aparicio OM, Zierath PD, Billington BL, Chablani SK, Gottschling DE (1993) Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage. Genes Dev 7:1133–1145PubMedCrossRefGoogle Scholar
  56. Sandell LL, Zakian VA (1993) Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell 75:729–739PubMedCrossRefGoogle Scholar
  57. Santangelo GM, Tornow J (1990) Efficient transcription of the glycolytic gene ADH1 and three translational components requires the GCR1 product, which can act through TUF/GRF/RAP binding sites. Mol Cell Biol 10:859–862PubMedGoogle Scholar
  58. Shore D, Nasmyth K (1987) Purification and cloning of a DNA binding protein from yeast that binds to both silencer and activator elements. Cell 51:721–732PubMedCrossRefGoogle Scholar
  59. Singer MS, Gottschling D (1994) TLC1: Template RNA component of Saccharomyces cerevisiae telomerase. Science 266:404–409PubMedCrossRefGoogle Scholar
  60. Sousa R, Arcangioli B (1989) A point mutation in the CYC1 UAS1 creates a new combination of regulatory elements that activate transcription synergistically. EMBO J 8:1801–1808PubMedGoogle Scholar
  61. Stanway CA, Chambers A, Kingsman AJ, Kingsman SM (1989) Characterization of the transcriptional potency of the subelements of the UAS of the yeast PGK gene in PGK minipromoter. Nucleic Acids Res 17:9205–9218PubMedCrossRefGoogle Scholar
  62. Stanway CA, Gibbs JM, Kearsey SE, Lopez MC, Baker HV (1994) The yeast coactivator GAL11 positively influences transcription of the PGK gene, but only when RAP1 is bound to its upstream activation sequence. Mol Gen Genet 243:207–214PubMedGoogle Scholar
  63. Stavenhagen JB, Zakian VA (1994) Internal tracts of telomeric DNA acts as silencers in S. cerevisiae. Genes Dev 8:1411–1422PubMedCrossRefGoogle Scholar
  64. Sussel L, Shore D (1991) Separation of transcriptional activation and silencing functions of the RAP1-encoded repressor/activator protein 1: Isolation of viable mutants affecting both silencing and telomere length. Proc Natl Acad Sci USA 88:7749–7753PubMedCrossRefGoogle Scholar
  65. Szostak JW, Orr-Weaver TL, Rothstein RJ, Stahl FW (1983) The double-strand break repair model for recombination. Cell 33:25–35PubMedCrossRefGoogle Scholar
  66. Thompson JS, Johnson LM, Grunstein M (1994) Specific repression of the yeast silent mating type locus HMR by an adjacent telomere. Mol Cell Biol 14:446–455PubMedGoogle Scholar
  67. Tornow J, Zeng X, Gao W, Santangelo GM (1993) GCR1, a transcriptional activator in S. cerevisiae, complexes with RAP1 and can function without its DNA binding domain. EMBO J 12:2431–2437PubMedGoogle Scholar
  68. Tsang JHS, Henry YAL, Chambers A, Kingsman AJ, Kingsman SM (1990) Phosphorylation influences the binding of the yeast RAP1 protein to the upstream activating sequence of the PGK gene. Nucleic Acids Res 18:7331–7337PubMedCrossRefGoogle Scholar
  69. Vignais ML, Huet J, Buhler JM, Sentenac A (1990) Contacts between the factor TUF and RPG sequences. J Biol Chem 265:14669–14674PubMedGoogle Scholar
  70. Vignais ML, Sentenac A (1989) Asymmetric DNA bending induced by the yeast multifunctional factor TUF. J Biol Chem 264:8463–8466PubMedGoogle Scholar
  71. Wellinger RJ, Wolf AJ, Zakian VA (1993) Saccharomyces telomeres acquire singlestrand TG1-3 tails late in S phase. Cell 72:51–60PubMedCrossRefGoogle Scholar
  72. White MA, Wierdl M, Detloff P, Petes TD (1991) DNA-binding protein RAP1 stimulates meiotic reombination at the HIS4 locus in yeast. Proc Natl Acad Sci USA 88:9755–9759PubMedCrossRefGoogle Scholar
  73. White MA, Detloff P, Strand M, Petes TD (1992) A promoter deletion reduces the rate of mitotic, but not meiotic, recombination at the HIS4 locus in yeast. Curr Genet 21:109–116PubMedCrossRefGoogle Scholar
  74. White MA, Dominska M, Petes TD (1993) Transcription factors are required for the meiotic recombination hotspot at the HIS4 locus in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 90:6621–6625PubMedCrossRefGoogle Scholar
  75. Wright JH, Gottschling DE, Zakian VA (1992) Saccharomyces telomeres assume a non-nucleosomal chromatin structure. Genes Dev 6:197–210PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • E. Gilson
    • 1
  • S. M. Gasser
    • 2
  1. 1.Ecole Normale Supérieure de LyonLyonFrance
  2. 2.ISREC (Swiss Institute for Experimental Cancer Research)EpalingesSwitzerland

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