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EMBO J. May 4, 1999; 18(9): 2522–2537.
PMCID: PMC1171334

Cohabitation of insulators and silencing elements in yeast subtelomeric regions.


In budding yeast, the telomeric DNA is flanked by a combination of two subtelomeric repetitive sequences, the X and Y' elements. We have investigated the influence of these sequences on telomeric silencing. The telomere-proximal portion of either X or Y' dampened silencing when located between the telomere and the reporter gene. These elements were named STARs, for subtelomeric anti-silencing regions. STARs can also counteract silencer-driven repression at the mating-type HML locus. When two STARs bracket a reporter gene, its expression is no longer influenced by surrounding silencing elements, although these are still active on a second reporter gene. In addition, an intervening STAR uncouples the silencing of neighboring genes. STARs thus display the hallmarks of insulators. Protection from silencing is recapitulated by multimerized oligonucleotides representing Tbf1p- and Reb1p-binding sites, as found in STARs. In contrast, sequences located more centromere proximal in X and Y' elements reinforce silencing. They can promote silencing downstream of an insulated expressed domain. Overall, our results suggest that the silencing emanating from telomeres can be propagated in a discontinuous manner via a series of subtelomeric relay elements.

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Selected References

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  • Aparicio OM, Gottschling DE. Overcoming telomeric silencing: a trans-activator competes to establish gene expression in a cell cycle-dependent way. Genes Dev. 1994 May 15;8(10):1133–1146. [PubMed]
  • Aparicio OM, Billington BL, Gottschling DE. Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae. Cell. 1991 Sep 20;66(6):1279–1287. [PubMed]
  • Bilaud T, Koering CE, Binet-Brasselet E, Ancelin K, Pollice A, Gasser SM, Gilson E. The telobox, a Myb-related telomeric DNA binding motif found in proteins from yeast, plants and human. Nucleic Acids Res. 1996 Apr 1;24(7):1294–1303. [PMC free article] [PubMed]
  • Boeke JD, LaCroute F, Fink GR. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–346. [PubMed]
  • Bonneaud N, Ozier-Kalogeropoulos O, Li GY, Labouesse M, Minvielle-Sebastia L, Lacroute F. A family of low and high copy replicative, integrative and single-stranded S. cerevisiae/E. coli shuttle vectors. Yeast. 1991 Aug-Sep;7(6):609–615. [PubMed]
  • Boscheron C, Maillet L, Marcand S, Tsai-Pflugfelder M, Gasser SM, Gilson E. Cooperation at a distance between silencers and proto-silencers at the yeast HML locus. EMBO J. 1996 May 1;15(9):2184–2195. [PMC free article] [PubMed]
  • Boulton SJ, Jackson SP. Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing. EMBO J. 1998 Mar 16;17(6):1819–1828. [PMC free article] [PubMed]
  • Braunstein M, Rose AB, Holmes SG, Allis CD, Broach JR. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes Dev. 1993 Apr;7(4):592–604. [PubMed]
  • Braunstein M, Sobel RE, Allis CD, Turner BM, Broach JR. Efficient transcriptional silencing in Saccharomyces cerevisiae requires a heterochromatin histone acetylation pattern. Mol Cell Biol. 1996 Aug;16(8):4349–4356. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Blue C, Marcand S, Gilson E. Proteins that bind to double-stranded regions of telomeric DNA. Trends Cell Biol. 1997 Aug;7(8):317–324. [PubMed]
  • Burns N, Grimwade B, Ross-Macdonald PB, Choi EY, Finberg K, Roeder GS, Snyder M. Large-scale analysis of gene expression, protein localization, and gene disruption in Saccharomyces cerevisiae. Genes Dev. 1994 May 1;8(9):1087–1105. [PubMed]
  • Cai H, Levine M. Modulation of enhancer-promoter interactions by insulators in the Drosophila embryo. Nature. 1995 Aug 10;376(6540):533–536. [PubMed]
  • Carlson M, Celenza JL, Eng FJ. Evolution of the dispersed SUC gene family of Saccharomyces by rearrangements of chromosome telomeres. Mol Cell Biol. 1985 Nov;5(11):2894–2902. [PMC free article] [PubMed]
  • Chasman DI, Lue NF, Buchman AR, LaPointe JW, Lorch Y, Kornberg RD. A yeast protein that influences the chromatin structure of UASG and functions as a powerful auxiliary gene activator. Genes Dev. 1990 Apr;4(4):503–514. [PubMed]
  • Chien CT, Buck S, Sternglanz R, Shore D. Targeting of SIR1 protein establishes transcriptional silencing at HM loci and telomeres in yeast. Cell. 1993 Nov 5;75(3):531–541. [PubMed]
  • Chung JH, Whiteley M, Felsenfeld G. A 5' element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. Cell. 1993 Aug 13;74(3):505–514. [PubMed]
  • Chung JH, Bell AC, Felsenfeld G. Characterization of the chicken beta-globin insulator. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):575–580. [PMC free article] [PubMed]
  • Cockell M, Palladino F, Laroche T, Kyrion G, Liu C, Lustig AJ, Gasser SM. The carboxy termini of Sir4 and Rap1 affect Sir3 localization: evidence for a multicomponent complex required for yeast telomeric silencing. J Cell Biol. 1995 May;129(4):909–924. [PMC free article] [PubMed]
  • Lyon MF. The quest for the X-inactivation centre. Trends Genet. 1991 Mar;7(3):69–70. [PubMed]
  • Dujon B. The yeast genome project: what did we learn? Trends Genet. 1996 Jul;12(7):263–270. [PubMed]
  • Elble R. A simple and efficient procedure for transformation of yeasts. Biotechniques. 1992 Jul;13(1):18–20. [PubMed]
  • Enomoto S, Longtine MS, Berman J. Enhancement of telomere-plasmid segregation by the X-telomere associated sequence in Saccharomyces cerevisiae involves SIR2, SIR3, SIR4 and ABF1. Genetics. 1994 Mar;136(3):757–767. [PMC free article] [PubMed]
  • Fritze CE, Verschueren K, Strich R, Easton Esposito R. Direct evidence for SIR2 modulation of chromatin structure in yeast rDNA. EMBO J. 1997 Nov 3;16(21):6495–6509. [PMC free article] [PubMed]
  • Gerasimova TI, Corces VG. Boundary and insulator elements in chromosomes. Curr Opin Genet Dev. 1996 Apr;6(2):185–192. [PubMed]
  • Glover DM, Leibowitz MH, McLean DA, Parry H. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell. 1995 Apr 7;81(1):95–105. [PubMed]
  • Gotta M, Laroche T, Formenton A, Maillet L, Scherthan H, Gasser SM. The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild-type Saccharomyces cerevisiae. J Cell Biol. 1996 Sep;134(6):1349–1363. [PMC free article] [PubMed]
  • Gotta M, Strahl-Bolsinger S, Renauld H, Laroche T, Kennedy BK, Grunstein M, Gasser SM. Localization of Sir2p: the nucleolus as a compartment for silent information regulators. EMBO J. 1997 Jun 2;16(11):3243–3255. [PMC free article] [PubMed]
  • Gottschling DE, Aparicio OM, Billington BL, Zakian VA. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell. 1990 Nov 16;63(4):751–762. [PubMed]
  • Gravel S, Larrivée M, Labrecque P, Wellinger RJ. Yeast Ku as a regulator of chromosomal DNA end structure. Science. 1998 May 1;280(5364):741–744. [PubMed]
  • Hecht A, Laroche T, Strahl-Bolsinger S, Gasser SM, Grunstein M. Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell. 1995 Feb 24;80(4):583–592. [PubMed]
  • Hecht A, Strahl-Bolsinger S, Grunstein M. Spreading of transcriptional repressor SIR3 from telomeric heterochromatin. Nature. 1996 Sep 5;383(6595):92–96. [PubMed]
  • Kellum R, Schedl P. A group of scs elements function as domain boundaries in an enhancer-blocking assay. Mol Cell Biol. 1992 May;12(5):2424–2431. [PMC free article] [PubMed]
  • Kim RA, Caron PR, Wang JC. Effects of yeast DNA topoisomerase III on telomere structure. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2667–2671. [PMC free article] [PubMed]
  • Kondo T, Zákány J, Duboule D. Control of colinearity in AbdB genes of the mouse HoxD complex. Mol Cell. 1998 Jan;1(2):289–300. [PubMed]
  • Künzler M, Braus GH, Georgiev O, Seipel K, Schaffner W. Functional differences between mammalian transcription activation domains at the yeast GAL1 promoter. EMBO J. 1994 Feb 1;13(3):641–645. [PMC free article] [PubMed]
  • Lamond AI, Earnshaw WC. Structure and function in the nucleus. Science. 1998 Apr 24;280(5363):547–553. [PubMed]
  • Laroche T, Martin SG, Gotta M, Gorham HC, Pryde FE, Louis EJ, Gasser SM. Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres. Curr Biol. 1998 May 21;8(11):653–656. [PubMed]
  • Liaw PC, Brandl CJ. Defining the sequence specificity of the Saccharomyces cerevisiae DNA binding protein REB1p by selecting binding sites from random-sequence oligonucleotides. Yeast. 1994 Jun;10(6):771–787. [PubMed]
  • Liu ZP, Tye BK. A yeast protein that binds to vertebrate telomeres and conserved yeast telomeric junctions. Genes Dev. 1991 Jan;5(1):49–59. [PubMed]
  • Longtine MS, Enomoto S, Finstad SL, Berman J. Yeast telomere repeat sequence (TRS) improves circular plasmid segregation, and TRS plasmid segregation involves the RAP1 gene product. Mol Cell Biol. 1992 May;12(5):1997–2009. [PMC free article] [PubMed]
  • Longtine MS, Enomoto S, Finstad SL, Berman J. Telomere-mediated plasmid segregation in Saccharomyces cerevisiae involves gene products required for transcriptional repression at silencers and telomeres. Genetics. 1993 Feb;133(2):171–182. [PMC free article] [PubMed]
  • Louis EJ. The chromosome ends of Saccharomyces cerevisiae. Yeast. 1995 Dec;11(16):1553–1573. [PubMed]
  • Louis EJ, Borts RH. A complete set of marked telomeres in Saccharomyces cerevisiae for physical mapping and cloning. Genetics. 1995 Jan;139(1):125–136. [PMC free article] [PubMed]
  • Louis EJ, Haber JE. Mitotic recombination among subtelomeric Y' repeats in Saccharomyces cerevisiae. Genetics. 1990 Mar;124(3):547–559. [PMC free article] [PubMed]
  • Louis EJ, Haber JE. The structure and evolution of subtelomeric Y' repeats in Saccharomyces cerevisiae. Genetics. 1992 Jul;131(3):559–574. [PMC free article] [PubMed]
  • Louis EJ, Naumova ES, Lee A, Naumov G, Haber JE. The chromosome end in yeast: its mosaic nature and influence on recombinational dynamics. Genetics. 1994 Mar;136(3):789–802. [PMC free article] [PubMed]
  • Lustig AJ. Mechanisms of silencing in Saccharomyces cerevisiae. Curr Opin Genet Dev. 1998 Apr;8(2):233–239. [PubMed]
  • Mahoney DJ, Broach JR. The HML mating-type cassette of Saccharomyces cerevisiae is regulated by two separate but functionally equivalent silencers. Mol Cell Biol. 1989 Nov;9(11):4621–4630. [PMC free article] [PubMed]
  • Maillet L, Boscheron C, Gotta M, Marcand S, Gilson E, Gasser SM. Evidence for silencing compartments within the yeast nucleus: a role for telomere proximity and Sir protein concentration in silencer-mediated repression. Genes Dev. 1996 Jul 15;10(14):1796–1811. [PubMed]
  • Marcand S, Buck SW, Moretti P, Gilson E, Shore D. Silencing of genes at nontelomeric sites in yeast is controlled by sequestration of silencing factors at telomeres by Rap 1 protein. Genes Dev. 1996 Jun 1;10(11):1297–1309. [PubMed]
  • Marcand S, Gasser SM, Gilson E. Chromatin: a sticky silence. Curr Biol. 1996 Oct 1;6(10):1222–1225. [PubMed]
  • McLean M, Hubberstey AV, Bouman DJ, Pece N, Mastrangelo P, Wildeman AG. Organization of the Saccharomyces cerevisiae actin gene UAS: functional significance of reiterated REB1 binding sites and AT-rich elements. Mol Microbiol. 1995 Nov;18(4):605–614. [PubMed]
  • Mihaly J, Hogga I, Gausz J, Gyurkovics H, Karch F. In situ dissection of the Fab-7 region of the bithorax complex into a chromatin domain boundary and a Polycomb-response element. Development. 1997 May;124(9):1809–1820. [PubMed]
  • Moazed D, Kistler A, Axelrod A, Rine J, Johnson AD. Silent information regulator protein complexes in Saccharomyces cerevisiae: a SIR2/SIR4 complex and evidence for a regulatory domain in SIR4 that inhibits its interaction with SIR3. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2186–2191. [PMC free article] [PubMed]
  • Moretti P, Freeman K, Coodly L, Shore D. Evidence that a complex of SIR proteins interacts with the silencer and telomere-binding protein RAP1. Genes Dev. 1994 Oct 1;8(19):2257–2269. [PubMed]
  • Ness F, Aigle M. RTM1: a member of a new family of telomeric repeated genes in yeast. Genetics. 1995 Jul;140(3):945–956. [PMC free article] [PubMed]
  • Nimmo ER, Cranston G, Allshire RC. Telomere-associated chromosome breakage in fission yeast results in variegated expression of adjacent genes. EMBO J. 1994 Aug 15;13(16):3801–3811. [PMC free article] [PubMed]
  • Nugent CI, Bosco G, Ross LO, Evans SK, Salinger AP, Moore JK, Haber JE, Lundblad V. Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr Biol. 1998 May 21;8(11):657–660. [PubMed]
  • Ohtsuki S, Levine M. GAGA mediates the enhancer blocking activity of the eve promoter in the Drosophila embryo. Genes Dev. 1998 Nov 1;12(21):3325–3330. [PMC free article] [PubMed]
  • Pikaart MJ, Recillas-Targa F, Felsenfeld G. Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators. Genes Dev. 1998 Sep 15;12(18):2852–2862. [PMC free article] [PubMed]
  • Pirrotta V. PcG complexes and chromatin silencing. Curr Opin Genet Dev. 1997 Apr;7(2):249–258. [PubMed]
  • Pryde FE, Louis EJ. Limitations of silencing at native yeast telomeres. EMBO J. 1999 May 4;18(9):2538–2550. [PMC free article] [PubMed]
  • Renauld H, Aparicio OM, Zierath PD, Billington BL, Chhablani SK, Gottschling DE. Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage. Genes Dev. 1993 Jul;7(7A):1133–1145. [PubMed]
  • Roseman RR, Johnson EA, Rodesch CK, Bjerke M, Nagoshi RN, Geyer PK. A P element containing suppressor of hairy-wing binding regions has novel properties for mutagenesis in Drosophila melanogaster. Genetics. 1995 Nov;141(3):1061–1074. [PMC free article] [PubMed]
  • Rundlett SE, Carmen AA, Suka N, Turner BM, Grunstein M. Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3. Nature. 1998 Apr 23;392(6678):831–835. [PubMed]
  • Sandell LL, Gottschling DE, Zakian VA. Transcription of a yeast telomere alleviates telomere position effect without affecting chromosome stability. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12061–12065. [PMC free article] [PubMed]
  • Shei GJ, Broach JR. Yeast silencers can act as orientation-dependent gene inactivation centers that respond to environmental signals. Mol Cell Biol. 1995 Jul;15(7):3496–3506. [PMC free article] [PubMed]
  • Sherman JM, Pillus L. An uncertain silence. Trends Genet. 1997 Aug;13(8):308–313. [PubMed]
  • Stone EM, Swanson MJ, Romeo AM, Hicks JB, Sternglanz R. The SIR1 gene of Saccharomyces cerevisiae and its role as an extragenic suppressor of several mating-defective mutants. Mol Cell Biol. 1991 Apr;11(4):2253–2262. [PMC free article] [PubMed]
  • Strahl-Bolsinger S, Hecht A, Luo K, Grunstein M. SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev. 1997 Jan 1;11(1):83–93. [PubMed]
  • Thierry A, Fairhead C, Dujon B. The complete sequence of the 8.2 kb segment left of MAT on chromosome III reveals five ORFs, including a gene for a yeast ribokinase. Yeast. 1990 Nov-Dec;6(6):521–534. [PubMed]
  • Thompson JS, Johnson LM, Grunstein M. Specific repression of the yeast silent mating locus HMR by an adjacent telomere. Mol Cell Biol. 1994 Jan;14(1):446–455. [PMC free article] [PubMed]
  • Triolo T, Sternglanz R. Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature. 1996 May 16;381(6579):251–253. [PubMed]
  • Vega-Palas MA, Venditti S, Di Mauro E. Telomeric transcriptional silencing in a natural context. Nat Genet. 1997 Mar;15(3):232–233. [PubMed]
  • Wach A, Brachat A, Pöhlmann R, Philippsen P. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994 Dec;10(13):1793–1808. [PubMed]
  • Wakimoto BT. Beyond the nucleosome: epigenetic aspects of position-effect variegation in Drosophila. Cell. 1998 May 1;93(3):321–324. [PubMed]
  • Yamada M, Hayatsu N, Matsuura A, Ishikawa F. Y'-Help1, a DNA helicase encoded by the yeast subtelomeric Y' element, is induced in survivors defective for telomerase. J Biol Chem. 1998 Dec 11;273(50):33360–33366. [PubMed]

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