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. 2000 Feb;154(2):587–598. doi: 10.1093/genetics/154.2.587

Telomere structure regulates the heritability of repressed subtelomeric chromatin in Saccharomyces cerevisiae.

Y Park 1, A J Lustig 1
PMCID: PMC1460967  PMID: 10655213

Abstract

Telomeres, the protein-DNA structures present at the termini of linear chromosomes, are capable of conferring a reversible repression of Pol II- and Pol III-transcribed genes positioned in adjacent subtelomeric regions. This phenomenon, termed telomeric silencing, is likely to be the consequence of a more global telomere position effect at the level of chromatin structure. To understand the role of telomere structure in this position effect, we have developed an assay to distinguish between the heritability of transcriptionally repressed and derepressed states in yeast. We have previously demonstrated that an elongated telomeric tract leads to hyperrepression of telomere-adjacent genes. We show here that the predominant effect of elongated telomeres is to increase the inheritance of the repressed state in cis. Interestingly, the presence of elongated telomeres overcomes the partial requirement of yCAF-1 in silencing. We propose that the formation of a specific telomeric structure is necessary for the heritability of repressed subtelomeric chromatin.

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Selected References

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  1. Ansari A., Gartenberg M. R. Persistence of an alternate chromatin structure at silenced loci in vitro. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):343–348. doi: 10.1073/pnas.96.2.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aparicio O. M., Gottschling D. E. 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. doi: 10.1101/gad.8.10.1133. [DOI] [PubMed] [Google Scholar]
  3. Austriaco N. R., Jr, Guarente L. P. Changes of telomere length cause reciprocal changes in the lifespan of mother cells in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9768–9772. doi: 10.1073/pnas.94.18.9768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bi X., Broach J. R. DNA in transcriptionally silent chromatin assumes a distinct topology that is sensitive to cell cycle progression. Mol Cell Biol. 1997 Dec;17(12):7077–7087. doi: 10.1128/mcb.17.12.7077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Braunstein M., Rose A. B., Holmes S. G., Allis C. D., Broach J. R. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes Dev. 1993 Apr;7(4):592–604. doi: 10.1101/gad.7.4.592. [DOI] [PubMed] [Google Scholar]
  6. Buck S. W., Shore D. Action of a RAP1 carboxy-terminal silencing domain reveals an underlying competition between HMR and telomeres in yeast. Genes Dev. 1995 Feb 1;9(3):370–384. doi: 10.1101/gad.9.3.370. [DOI] [PubMed] [Google Scholar]
  7. Cockell M., Gotta M., Palladino F., Martin S. G., Gasser S. M. Targeting Sir proteins to sites of action: a general mechanism for regulated repression. Cold Spring Harb Symp Quant Biol. 1998;63:401–412. doi: 10.1101/sqb.1998.63.401. [DOI] [PubMed] [Google Scholar]
  8. Cockell M., Palladino F., Laroche T., Kyrion G., Liu C., Lustig A. J., Gasser S. M. 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. doi: 10.1083/jcb.129.4.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Enomoto S., McCune-Zierath P. D., Gerami-Nejad M., Sanders M. A., Berman J. RLF2, a subunit of yeast chromatin assembly factor-I, is required for telomeric chromatin function in vivo. Genes Dev. 1997 Feb 1;11(3):358–370. doi: 10.1101/gad.11.3.358. [DOI] [PubMed] [Google Scholar]
  10. Ferguson B. M., Brewer B. J., Reynolds A. E., Fangman W. L. A yeast origin of replication is activated late in S phase. Cell. 1991 May 3;65(3):507–515. doi: 10.1016/0092-8674(91)90468-e. [DOI] [PubMed] [Google Scholar]
  11. Fourel G., Revardel E., Koering C. E., Gilson E. Cohabitation of insulators and silencing elements in yeast subtelomeric regions. EMBO J. 1999 May 4;18(9):2522–2537. doi: 10.1093/emboj/18.9.2522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Game J. C., Kaufman P. D. Role of Saccharomyces cerevisiae chromatin assembly factor-I in repair of ultraviolet radiation damage in vivo. Genetics. 1999 Feb;151(2):485–497. doi: 10.1093/genetics/151.2.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gedvilaite A., Sasnauskas K. Control of the expression of the ADE2 gene of the yeast Saccharomyces cerevisiae. Curr Genet. 1994 Jun;25(6):475–479. doi: 10.1007/BF00351665. [DOI] [PubMed] [Google Scholar]
  14. Gotta M., Strahl-Bolsinger S., Renauld H., Laroche T., Kennedy B. K., Grunstein M., Gasser S. M. Localization of Sir2p: the nucleolus as a compartment for silent information regulators. EMBO J. 1997 Jun 2;16(11):3243–3255. doi: 10.1093/emboj/16.11.3243. [DOI] [PMC free article] [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. Telomere-proximal DNA in Saccharomyces cerevisiae is refractory to methyltransferase activity in vivo. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4062–4065. doi: 10.1073/pnas.89.9.4062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997 Sep 25;389(6649):349–352. doi: 10.1038/38664. [DOI] [PubMed] [Google Scholar]
  18. Hecht A., Laroche T., Strahl-Bolsinger S., Gasser S. M., 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. doi: 10.1016/0092-8674(95)90512-x. [DOI] [PubMed] [Google Scholar]
  19. Hecht A., Strahl-Bolsinger S., Grunstein M. Spreading of transcriptional repressor SIR3 from telomeric heterochromatin. Nature. 1996 Sep 5;383(6595):92–96. doi: 10.1038/383092a0. [DOI] [PubMed] [Google Scholar]
  20. Henikoff S. Dosage-dependent modification of position-effect variegation in Drosophila. Bioessays. 1996 May;18(5):401–409. doi: 10.1002/bies.950180510. [DOI] [PubMed] [Google Scholar]
  21. Holmes S. G., Broach J. R. Silencers are required for inheritance of the repressed state in yeast. Genes Dev. 1996 Apr 15;10(8):1021–1032. doi: 10.1101/gad.10.8.1021. [DOI] [PubMed] [Google Scholar]
  22. Kaufman P. D., Kobayashi R., Kessler N., Stillman B. The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication. Cell. 1995 Jun 30;81(7):1105–1114. doi: 10.1016/s0092-8674(05)80015-7. [DOI] [PubMed] [Google Scholar]
  23. Kennedy B. K., Gotta M., Sinclair D. A., Mills K., McNabb D. S., Murthy M., Pak S. M., Laroche T., Gasser S. M., Guarente L. Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae. Cell. 1997 May 2;89(3):381–391. doi: 10.1016/s0092-8674(00)80219-6. [DOI] [PubMed] [Google Scholar]
  24. Krude T. Chromatin replication: Finding the right connection. Curr Biol. 1999 Jun 3;9(11):R394–R396. doi: 10.1016/s0960-9822(99)80251-6. [DOI] [PubMed] [Google Scholar]
  25. Kurtz S., Shore D. RAP1 protein activates and silences transcription of mating-type genes in yeast. Genes Dev. 1991 Apr;5(4):616–628. doi: 10.1101/gad.5.4.616. [DOI] [PubMed] [Google Scholar]
  26. Kyrion G., Boakye K. A., Lustig A. J. C-terminal truncation of RAP1 results in the deregulation of telomere size, stability, and function in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Nov;12(11):5159–5173. doi: 10.1128/mcb.12.11.5159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Li B., Lustig A. J. A novel mechanism for telomere size control in Saccharomyces cerevisiae. Genes Dev. 1996 Jun 1;10(11):1310–1326. doi: 10.1101/gad.10.11.1310. [DOI] [PubMed] [Google Scholar]
  28. Liu C., Lustig A. J. Genetic analysis of Rap1p/Sir3p interactions in telomeric and HML silencing in Saccharomyces cerevisiae. Genetics. 1996 May;143(1):81–93. doi: 10.1093/genetics/143.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Liu C., Mao X., Lustig A. J. Mutational analysis defines a C-terminal tail domain of RAP1 essential for Telomeric silencing in Saccharomyces cerevisiae. Genetics. 1994 Dec;138(4):1025–1040. doi: 10.1093/genetics/138.4.1025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Loo S., Rine J. Silencing and heritable domains of gene expression. Annu Rev Cell Dev Biol. 1995;11:519–548. doi: 10.1146/annurev.cb.11.110195.002511. [DOI] [PubMed] [Google Scholar]
  31. Lustig A. J., Liu C., Zhang C., Hanish J. P. Tethered Sir3p nucleates silencing at telomeres and internal loci in Saccharomyces cerevisiae. Mol Cell Biol. 1996 May;16(5):2483–2495. doi: 10.1128/mcb.16.5.2483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Maillet L., Boscheron C., Gotta M., Marcand S., Gilson E., Gasser S. M. 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. doi: 10.1101/gad.10.14.1796. [DOI] [PubMed] [Google Scholar]
  33. Marcand S., Buck S. W., 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. doi: 10.1101/gad.10.11.1297. [DOI] [PubMed] [Google Scholar]
  34. Martin S. G., Laroche T., Suka N., Grunstein M., Gasser S. M. Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell. 1999 May 28;97(5):621–633. doi: 10.1016/s0092-8674(00)80773-4. [DOI] [PubMed] [Google Scholar]
  35. Mills K. D., Sinclair D. A., Guarente L. MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks. Cell. 1999 May 28;97(5):609–620. doi: 10.1016/s0092-8674(00)80772-2. [DOI] [PubMed] [Google Scholar]
  36. Monson E. K., de Bruin D., Zakian V. A. The yeast Cac1 protein is required for the stable inheritance of transcriptionally repressed chromatin at telomeres. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13081–13086. doi: 10.1073/pnas.94.24.13081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Park Y., Hanish J., Lustig A. J. Sir3p domains involved in the initiation of telomeric silencing in Saccharomyces cerevisiae. Genetics. 1998 Nov;150(3):977–986. doi: 10.1093/genetics/150.3.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pillus L., Rine J. Epigenetic inheritance of transcriptional states in S. cerevisiae. Cell. 1989 Nov 17;59(4):637–647. doi: 10.1016/0092-8674(89)90009-3. [DOI] [PubMed] [Google Scholar]
  39. Pryde F. E., Louis E. J. Limitations of silencing at native yeast telomeres. EMBO J. 1999 May 4;18(9):2538–2550. doi: 10.1093/emboj/18.9.2538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Qian Z., Huang H., Hong J. Y., Burck C. L., Johnston S. D., Berman J., Carol A., Liebman S. W. Yeast Ty1 retrotransposition is stimulated by a synergistic interaction between mutations in chromatin assembly factor I and histone regulatory proteins. Mol Cell Biol. 1998 Aug;18(8):4783–4792. doi: 10.1128/mcb.18.8.4783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Renauld H., Aparicio O. M., Zierath P. D., Billington B. L., Chhablani S. K., Gottschling D. E. 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. doi: 10.1101/gad.7.7a.1133. [DOI] [PubMed] [Google Scholar]
  42. Shibahara K., Stillman B. Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin. Cell. 1999 Feb 19;96(4):575–585. doi: 10.1016/s0092-8674(00)80661-3. [DOI] [PubMed] [Google Scholar]
  43. Sinclair D. A., Mills K., Guarente L. Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants. Science. 1997 Aug 29;277(5330):1313–1316. doi: 10.1126/science.277.5330.1313. [DOI] [PubMed] [Google Scholar]
  44. Smith J. S., Caputo E., Boeke J. D. A genetic screen for ribosomal DNA silencing defects identifies multiple DNA replication and chromatin-modulating factors. Mol Cell Biol. 1999 Apr;19(4):3184–3197. doi: 10.1128/mcb.19.4.3184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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. doi: 10.1101/gad.11.1.83. [DOI] [PubMed] [Google Scholar]
  46. Sussel L., Vannier D., Shore D. Epigenetic switching of transcriptional states: cis- and trans-acting factors affecting establishment of silencing at the HMR locus in Saccharomyces cerevisiae. Mol Cell Biol. 1993 Jul;13(7):3919–3928. doi: 10.1128/mcb.13.7.3919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Vega-Palas M. A., Venditti S., Di Mauro E. Telomeric transcriptional silencing in a natural context. Nat Genet. 1997 Mar;15(3):232–233. doi: 10.1038/ng0397-232. [DOI] [PubMed] [Google Scholar]
  48. 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]

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