Advertisement

Chromosomal Position Effect and Aging

  • Eric Gilson
  • Frédérique Magdinier

Abstract

Aging is a complex biological process that manifests through cellular, physical, and metabolic changes in all types of tissues. Changes in chromosome structure and function throughout life play a pivotal role in this irreversible physiological process by affecting gene expression, replication, recombination, DNA repair, and epigenetic programming. Upon exogenous stress or simply as the result of cellular metabolism and cellular division, DNA rearrangements or redistribution of epigenetic factors might alter the chromatin environment and expression of genes regulating the aging process by the so-called chromosomal position effect. These changes can vary from cell to cell and can be associated with variegated pattern of gene expression. We will discuss here what is known on the mechanisms of various types of chromosomal position effects and their consequences on the aging process.

Keywords

Chromosomal position effect Telomeric position effect Epigenetics Aging Telomeres Chromatin 

References

  1. Abdallah P, Luciano P, Runge K, Lisby M, Geli V, Gilson E, Teixera T. A two step model for senescence triggered by a single critically short telomere, Nature Cell Biology. In press.Google Scholar
  2. Aguilaniu H, Gustafsson L, Rigoulet M, Nystrom T (2003) Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. Science 299: 1751–3PubMedCrossRefGoogle Scholar
  3. Ai W, Bertram PG, Tsang CK, Chan TF, Zheng XF (2002) Regulation of subtelomeric silencing during stress response. Mol Cell 10: 1295–305PubMedCrossRefGoogle Scholar
  4. Alcedo J, Kenyon C (2004) Regulation of C. elegans longevity by specific gustatory and olfactory neurons. Neuron 41: 45–55PubMedCrossRefGoogle Scholar
  5. Allman D, Miller JP (2005a) B cell development and receptor diversity during aging. Curr Opin Immunol 17: 463–7PubMedCrossRefGoogle Scholar
  6. Allman D, Miller JP (2005b) The aging of early B-cell precursors. Immunol Rev 205: 18–29PubMedCrossRefGoogle Scholar
  7. Apfeld J, Kenyon C (1999) Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402: 804–9PubMedCrossRefGoogle Scholar
  8. Araki T, Sasaki Y, Milbrandt J (2004) Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305: 1010–3PubMedCrossRefGoogle Scholar
  9. AS IJ, Greider CW (2003) Short telomeres induce a DNA damage response in Saccharomyces cerevisiae. Mol Biol Cell 14: 987–1001CrossRefGoogle Scholar
  10. Au WY, Ma ES, Lam VM, Chan JL, Pang A, Kwong YL (2004) Glucose 6-phosphate dehydrogenase (G6PD) deficiency in elderly Chinese women heterozygous for G6PD variants. Am J Med Genet A 129A: 208–11PubMedCrossRefGoogle Scholar
  11. Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J (2007) Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318: 798–801PubMedCrossRefGoogle Scholar
  12. Bahar R, Hartmann CH, Rodriguez KA, Denny AD, Busuttil RA, Dolle ME, Calder RB, Chisholm GB, Pollock BH, Klein CA, Vijg J (2006) Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature 441: 1011–4PubMedCrossRefGoogle Scholar
  13. Barry JD, Ginger ML, Burton P, McCulloch R (2003) Why are parasite contingency genes often associated with telomeres? Int J Parasitol 33: 29–45PubMedCrossRefGoogle Scholar
  14. Baur JA, Zou Y, Shay JW, Wright WE (2001) Telomere position effect in human cells. Science 292: 2075–7PubMedCrossRefGoogle Scholar
  15. Benetti R, Garcia-Cao M, Blasco MA (2007a) Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat Genet 39: 243–50PubMedCrossRefGoogle Scholar
  16. Benetti R, Gonzalo S, Jaco I, Schotta G, Klatt P, Jenuwein T, Blasco MA (2007b) Suv4-20 h deficiency results in telomere elongation and derepression of telomere recombination. J Cell Biol 178: 925–36PubMedCrossRefGoogle Scholar
  17. Blackwell C, Martin KA, Greenall A, Pidoux A, Allshire RC, Whitehall SK (2004) The Schizosaccharomyces pombe HIRA-like protein Hip1 is required for the periodic expression of histone genes and contributes to the function of complex centromeres. Mol Cell Biol 24: 4309–20PubMedCrossRefGoogle Scholar
  18. Blasco MA (2007a) Telomere length, stem cells and aging. Nat Chem Biol 3: 640–9PubMedCrossRefGoogle Scholar
  19. Blasco MA (2007b) The epigenetic regulation of mammalian telomeres. Nat Rev Genet 8: 299–309PubMedCrossRefGoogle Scholar
  20. Borst P, Ulbert S (2001) Control of VSG gene expression sites. Mol Biochem Parasitol 114: 17–27PubMedCrossRefGoogle Scholar
  21. Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G (2006) Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 127: 1361–73PubMedCrossRefGoogle Scholar
  22. Buck SW, Shore D (1995) Action of a RAP1 carboxy-terminal silencing domain reveals an underlying competition between HMR and telomeres in yeast. Genes Dev 9: 370–84PubMedCrossRefGoogle Scholar
  23. Busque L, Mio R, Mattioli J, Brais E, Blais N, Lalonde Y, Maragh M, Gilliland DG (1996) Nonrandom X-inactivation patterns in normal females: lyonization ratios vary with age. Blood 88: 59–65PubMedGoogle Scholar
  24. Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120: 513–22PubMedCrossRefGoogle Scholar
  25. Canela A, Vera E, Klatt P, Blasco MA (2007) High-throughput telomere length quantification by FISH and its application to human population studies. Proc Natl Acad Sci USA 104: 5300–5PubMedCrossRefGoogle Scholar
  26. Cawthon RM, Smith KR, O'Brien E, Sivatchenko A, Kerber RA (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361: 393–5PubMedCrossRefGoogle Scholar
  27. Cazzola M, May A, Bergamaschi G, Cerani P, Rosti V, Bishop DF (2000) Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anemia in carrier females. Blood 96: 4363–5PubMedGoogle Scholar
  28. Chambers SM, Shaw CA, Gatza C, Fisk CJ, Donehower LA, Goodell MA (2007) Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol 5: e201PubMedCrossRefGoogle Scholar
  29. Chang S, Multani AS, Cabrera NG, Naylor ML, Laud P, Lombard D, Pathak S, Guarente L, DePinho RA (2004) Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet 36: 877–82PubMedCrossRefGoogle Scholar
  30. Cherkas LF, Aviv A, Valdes AM, Hunkin JL, Gardner JP, Surdulescu GL, Kimura M, Spector TD (2006) The effects of social status on biological aging as measured by white-blood-cell telomere length. Aging Cell 5: 361–5PubMedCrossRefGoogle Scholar
  31. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305: 390–2PubMedCrossRefGoogle Scholar
  32. d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP, Jackson SP (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426: 194–8PubMedCrossRefGoogle Scholar
  33. Dali-Youcef N, Lagouge M, Froelich S, Koehl C, Schoonjans K, Auwerx J (2007) Sirtuins: the `magnificent seven’, function, metabolism and longevity. Ann Med 39: 335–45PubMedCrossRefGoogle Scholar
  34. Daniel J (2005) Sir-dependent downregulation of various aging processes. Mol Genet Genomics 274: 539–47PubMedCrossRefGoogle Scholar
  35. de Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19: 2100–10PubMedCrossRefGoogle Scholar
  36. de Lange T, Shiue L, Myers RM, Cox DR, Naylor SL, Killery AM, Varmus HE (1990) Structure and variability of human chromosome ends. Mol Cell Biol 10: 518–27PubMedGoogle Scholar
  37. De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, Lyonnet S, Stewart CL, Munnich A, Le Merrer M, Levy N (2003) Lamin a truncation in Hutchinson-Gilford progeria. Science 300: 2055PubMedCrossRefGoogle Scholar
  38. Dreesen O, Li B, Cross GA (2007) Telomere structure and function in trypanosomes: a proposal. Nat Rev Microbiol 5: 70–5PubMedCrossRefGoogle Scholar
  39. Eissenberg JC, James TC, Foster-Hartnett DM, Hartnett T, Ngan V, Elgin SC (1990) Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster. Proc Natl Acad Sci USA 87: 9923–7PubMedCrossRefGoogle Scholar
  40. Enomoto S, Glowczewski L, Berman J (2002) MEC3, MEC1, and DDC2 are essential components of a telomere checkpoint pathway required for cell cycle arrest during senescence in Saccharomyces cerevisiae. Mol Biol Cell 13: 2626–38PubMedCrossRefGoogle Scholar
  41. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM (2004) Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci USA 101: 17312–5PubMedCrossRefGoogle Scholar
  42. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423: 293–8PubMedCrossRefGoogle Scholar
  43. Eugster A, Lanzuolo C, Bonneton M, Luciano P, Pollice A, Pulitzer JF, Stegberg E, Berthiau AS, Forstemann K, Corda Y, Lingner J, Geli V, Gilson E (2006) The finger subdomain of yeast telomerase cooperates with Pif1p to limit telomere elongation. Nat Struct Mol Biol 13: 734–9PubMedCrossRefGoogle Scholar
  44. Falcon AA, Aris JP (2003) Plasmid accumulation reduces life span in Saccharomyces cerevisiae. J Biol Chem 278: 41607–17PubMedCrossRefGoogle Scholar
  45. Feil R (2006) Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res 600: 46–57PubMedGoogle Scholar
  46. Festenstein R, Sharghi-Namini S, Fox M, Roderick K, Tolaini M, Norton T, Saveliev A, Kioussis D, Singh P (1999) Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context-dependent manner. Nat Genet 23: 457–61PubMedCrossRefGoogle Scholar
  47. Fourel G, Magdinier F, Gilson E (2004) Insulator dynamics and the setting of chromatin domains. Bioessays 26: 523–32PubMedCrossRefGoogle Scholar
  48. Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23: 413–8PubMedCrossRefGoogle Scholar
  49. Fraser HB, Khaitovich P, Plotkin JB, Paabo S, Eisen MB (2005) Aging and gene expression in the primate brain. PLoS Biol 3: e274PubMedCrossRefGoogle Scholar
  50. Funayama R, Ishikawa F (2007) Cellular senescence and chromatin structure. Chromosoma 116: 431–40PubMedCrossRefGoogle Scholar
  51. Funayama R, Saito M, Tanobe H, Ishikawa F (2006) Loss of linker histone H1 in cellular senescence. J Cell Biol 175: 869–80PubMedCrossRefGoogle Scholar
  52. Gale RE, Fielding AK, Harrison CN, Linch DC (1997) Acquired skewing of X-chromosome inactivation patterns in myeloid cells of the elderly suggests stochastic clonal loss with age. Br J Haematol 98: 512–9PubMedCrossRefGoogle Scholar
  53. Garcia-Cao M, O’Sullivan R, Peters AH, Jenuwein T, Blasco MA (2004) Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat Genet 36: 94–9PubMedCrossRefGoogle Scholar
  54. Gartenberg MR, Neumann FR, Laroche T, Blaszczyk M, Gasser SM (2004) Sir-mediated repression can occur independently of chromosomal and subnuclear contexts. Cell 119: 955–67PubMedCrossRefGoogle Scholar
  55. Gaszner M, Felsenfeld G (2006) Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet 7: 703–13PubMedCrossRefGoogle Scholar
  56. Gaubatz JW, Cutler RG (1990) Mouse satellite DNA is transcribed in senescent cardiac muscle. J Biol Chem 265: 17753–8PubMedGoogle Scholar
  57. Gaubatz JW, Flores SC (1990) Tissue-specific and age-related variations in repetitive sequences of mouse extrachromosomal circular DNAs. Mutat Res 237: 29–36PubMedGoogle Scholar
  58. Gilson E, Geli V (2007) How telomeres are replicated. Nat Rev Mol Cell Biol 8: 825–38PubMedCrossRefGoogle Scholar
  59. Girton JR, Johansen KM (2008) Chromatin structure and the regulation of gene expression: the lessons of PEV in Drosophila. Adv Genet 61: 1–43PubMedCrossRefGoogle Scholar
  60. Gonzalo S, Garcia-Cao M, Fraga MF, Schotta G, Peters AH, Cotter SE, Eguia R, Dean DC, Esteller M, Jenuwein T, Blasco MA (2005) Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol 7: 420–8PubMedCrossRefGoogle Scholar
  61. Gonzalo S, Jaco I, Fraga MF, Chen T, Li E, Esteller M, Blasco MA (2006) DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol 8: 416–24PubMedCrossRefGoogle Scholar
  62. Gotta M, Laroche T, Formenton A, Maillet L, Scherthan H, Gasser SM (1996) The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild-type Saccharomyces cerevisiae. J Cell Biol 134: 1349–63PubMedCrossRefGoogle Scholar
  63. Gottschling DE, Aparicio OM, Billington BL, Zakian VA (1990) Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell 63: 751–62PubMedCrossRefGoogle Scholar
  64. Greenall A, Williams ES, Martin KA, Palmer JM, Gray J, Liu C, Whitehall SK (2006) Hip3 interacts with the HIRA proteins Hip1 and Slm9 and is required for transcriptional silencing and accurate chromosome segregation. J Biol Chem 281: 8732–9PubMedCrossRefGoogle Scholar
  65. Haigis MC, Guarente LP (2006) Mammalian sirtuins – emerging roles in physiology, aging, and calorie restriction. Genes Dev 20: 2913–21PubMedCrossRefGoogle Scholar
  66. Halme A, Bumgarner S, Styles C, Fink GR (2004) Genetic and epigenetic regulation of the FLO gene family generates cell-surface variation in yeast. Cell 116: 405–15PubMedCrossRefGoogle Scholar
  67. Hansen KR, Burns G, Mata J, Volpe TA, Martienssen RA, Bahler J, Thon G (2005) Global effects on gene expression in fission yeast by silencing and RNA interference machineries. Mol Cell Biol 25: 590–601PubMedCrossRefGoogle Scholar
  68. Hatakeyama C, Anderson CL, Beever CL, Penaherrera MS, Brown CJ, Robinson WP (2004) The dynamics of X-inactivation skewing as women age. Clin Genet 66: 327–32PubMedCrossRefGoogle Scholar
  69. Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37: 614–36PubMedCrossRefGoogle Scholar
  70. Hediger F, Gasser SM (2002) Nuclear organization and silencing: putting things in their place. Nat Cell Biol 4: E53–5PubMedCrossRefGoogle Scholar
  71. Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM (2006) Cellular senescence in aging primates. Science 311: 1257PubMedCrossRefGoogle Scholar
  72. Hoppe GJ, Tanny JC, Rudner AD, Gerber SA, Danaie S, Gygi SP, Moazed D (2002) Steps in assembly of silent chromatin in yeast: Sir3-independent binding of a Sir2/Sir4 complex to silencers and role for Sir2-dependent deacetylation. Mol Cell Biol 22: 4167–80PubMedCrossRefGoogle Scholar
  73. Hsu CP, Odewale I, Alcendor RR, Sadoshima J (2008) Sirt1 protects the heart from aging and stress. Biol Chem 389: 221–31PubMedCrossRefGoogle Scholar
  74. Huyen Y, Zgheib O, Ditullio RA, Jr., Gorgoulis VG, Zacharatos P, Petty TJ, Sheston EA, Mellert HS,i Stavridi ES, Halazonetis TD (2004) Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432: 406–11PubMedCrossRefGoogle Scholar
  75. Invernizzi P, Pasini S, Selmi C, Miozzo M, Podda M (2008) Skewing of X chromosome inactivation in autoimmunity. Autoimmunity 41: 272–7PubMedCrossRefGoogle Scholar
  76. James TC, Elgin SC (1986) Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene. Mol Cell Biol 6: 3862–72PubMedGoogle Scholar
  77. Jeyapalan JC, Ferreira M, Sedivy JM, Herbig U (2007) Accumulation of senescent cells in mitotic tissue of aging primates. Mech Ageing Dev 128: 36–44PubMedCrossRefGoogle Scholar
  78. Kaeberleion M, McVey M, Guareute L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev, Vol 13 issue 9. Pages 2570–80. 1999Google Scholar
  79. Kaeberlein M, Kennedy BK (2005) Large-scale identification in yeast of conserved ageing genes. Mech Ageing Dev 126: 17–21PubMedCrossRefGoogle Scholar
  80. Karow JK, Wu L, Hickson ID (2000) RecQ family helicases: roles in cancer and aging. Curr Opin Genet Dev 10: 32–8PubMedCrossRefGoogle Scholar
  81. Kaufman PD, Cohen JL, Osley MA (1998) Hir proteins are required for position-dependent gene silencing in Saccharomyces cerevisiae in the absence of chromatin assembly factor I. Mol Cell Biol 18: 4793–806PubMedGoogle Scholar
  82. Kennedy BK, Austriaco NR, Jr., Zhang J, Guarente L (1995) Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 80: 485–96PubMedCrossRefGoogle Scholar
  83. Kennedy BK, Gotta M, Sinclair DA, Mills K, McNabb DS, Murthy M, Pak SM, Laroche T, Gasser SM, Guarente L (1997) Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae. Cell 89: 381–91PubMedCrossRefGoogle Scholar
  84. Kenyon C (2005) The plasticity of aging: insights from long-lived mutants. Cell 120: 449–60PubMedCrossRefGoogle Scholar
  85. Kim S, Benguria A, Lai CY, Jazwinski SM (1999) Modulation of life-span by histone deacetylase genes in Saccharomyces cerevisiae. Mol Biol Cell 10: 3125–36PubMedGoogle Scholar
  86. Kimura A, Umehara T, Horikoshi M (2002) Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing. Nat Genet 32: 370–7PubMedCrossRefGoogle Scholar
  87. Klar AJ, Fogel S, Macleod K (1979) MAR1-a regulator of the HMa and HMalpha Loci in Saccharomyces Cerevisiae. Genetics 93: 37–50PubMedGoogle Scholar
  88. Koering CE, Pollice A, Zibella MP, Bauwens S, Puisieux A, Brunori M, Brun C, Martins L, Sabatier L, Pulitzer JF, Gilson E (2002) Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity. EMBO Rep 3: 1055–61PubMedCrossRefGoogle Scholar
  89. Krabbe KS, Pedersen M, Bruunsgaard H (2004) Inflammatory mediators in the elderly. Exp Gerontol 39: 687–99PubMedCrossRefGoogle Scholar
  90. Kristiansen M, Knudsen GP, Bathum L, Naumova AK, Sorensen TI, Brix TH, Svendsen AJ, Christensen K, Kyvik KO, Orstavik KH (2005) Twin study of genetic and aging effects on X chromosome inactivation. Eur J Hum Genet 13: 599–606PubMedCrossRefGoogle Scholar
  91. Kyrion G, Liu K, Liu C, Lustig AJ (1993) RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. Genes Dev 7: 1146–59PubMedCrossRefGoogle Scholar
  92. Lee SK, Johnson RE, Yu SL, Prakash L, Prakash S (1999) Requirement of yeast SGS1 and SRS2 genes for replication and transcription. Science 286: 2339–42PubMedCrossRefGoogle Scholar
  93. Lezhava T (2001) Chromosome and aging: genetic conception of aging. Biogerontology 2: 253–60PubMedCrossRefGoogle Scholar
  94. Lezhava T, Jokhadze T (2007) Activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals. Ann NY Acad Sci 1100: 387–99PubMedCrossRefGoogle Scholar
  95. Libert S, Zwiener J, Chu X, Vanvoorhies W, Roman G, Pletcher SD (2007) Regulation of Drosophila life span by olfaction and food-derived odors. Science 315: 1133–7PubMedCrossRefGoogle Scholar
  96. Lindemann B (2001) Receptors and transduction in taste. Nature 413: 219–25PubMedCrossRefGoogle Scholar
  97. Lombardi G, Di Somma C, Rota F, Colao A (2005) Associated hormonal decline in aging: is there a role for GH therapy in aging men? J Endocrinol Invest 28: 99–108PubMedGoogle Scholar
  98. Lowell JE, Roughton AI, Lundblad V, Pillus L (2003) Telomerase-independent proliferation is influenced by cell type in Saccharomyces cerevisiae. Genetics 164: 909–21PubMedGoogle Scholar
  99. Lundblad V, Blackburn EH (1993) An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell 73: 347–60PubMedCrossRefGoogle Scholar
  100. Maillet L, Boscheron C, Gotta M, Marcand S, Gilson E, Gasser SM (1996a) Evidence for silencing compartments within the yeast nucleus: a role for telomere proximity and Sir protein concentration in silencer-mediated repression. Genes Dev 10: 1796–811PubMedCrossRefGoogle Scholar
  101. Maillet L, Boscheron C, Gotta M, Marcand S, Gilson E, Gasser SM (1996b) Evidence for silencing compartments within the yeast nucleus: a role for telomere proximity and Sir protein concentration in silencer-mediated repression. Genes Develop 10: 1796–811PubMedCrossRefGoogle Scholar
  102. Maillet L, Gaden F, Brevet V, Fourel G, Martin SG, Dubrana K, Gasser SM, Gilson E (2001) Ku-deficient yeast strains exhibit alternative states of silencing competence. EMBO Rep 2: 203–10PubMedCrossRefGoogle Scholar
  103. Makarov VL, Lejnine S, Bedoyan J, Langmore JP (1993) Nucleosomal organization of telomere-specific chromatin in rat. Cell 73: 775–87PubMedCrossRefGoogle Scholar
  104. Marcand S, Buck SW, Moretti P, Gilson E, Shore D (1996) Silencing of genes at nontelomeric sites in yeast is controlled by sequestration of silencing factors at telomeres by Rap 1 protein. Genes Dev 10: 1297–309PubMedCrossRefGoogle Scholar
  105. Martin GM (2005) Genetic modulation of senescent phenotypes in Homo sapiens. Cell 120: 523–32PubMedCrossRefGoogle Scholar
  106. Martin SG, Laroche T, Suka N, Grunstein M, Gasser SM (1999) Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell 97: 621–33PubMedCrossRefGoogle Scholar
  107. McAinsh AD, Scott-Drew S, Murray JA, Jackson SP (1999) DNA damage triggers disruption of telomeric silencing and Mec1p-dependent relocation of Sir3p. Curr Biol 9: 963–6PubMedCrossRefGoogle Scholar
  108. Mefford HC, Trask BJ (2002) The complex structure and dynamic evolution of human subtelomeres. Nat Rev Genet 3: 91–102PubMedCrossRefGoogle Scholar
  109. Michan S, Sinclair D (2007) Sirtuins in mammals: insights into their biological function. Biochem J 404: 1–13PubMedCrossRefGoogle Scholar
  110. Michishita E, McCord RA, Berber E, Kioi M, Padilla-Nash H, Damian M, Cheung P, Kusumoto R, Kawahara TL, Barrett JC, Chang HY, Bohr VA, Ried T, Gozani O, Chua KF (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452: 492–6PubMedCrossRefGoogle Scholar
  111. Mills KD, Sinclair DA, Guarente L (1999) MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks. Cell 97: 609–20PubMedCrossRefGoogle Scholar
  112. Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124: 315–29PubMedCrossRefGoogle Scholar
  113. Murciano C, Villamon E, Yanez A, O’Connor JE, Gozalbo D, Gil ML (2006) Impaired immune response to Candida albicans in aged mice. J Med Microbiol 55: 1649–56PubMedCrossRefGoogle Scholar
  114. Narita M, Krizhanovsky V, Nunez S, Chicas A, Hearn SA, Myers MP, Lowe SW (2006) A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell 126: 503–14PubMedCrossRefGoogle Scholar
  115. Narita M, Nunez S, Heard E, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113: 703–16PubMedCrossRefGoogle Scholar
  116. Ning Y, Xu JF, Li Y, Chavez L, Riethman HC, Lansdorp PM, Weng NP (2003) Telomere length and the expression of natural telomeric genes in human fibroblasts. Hum Mol Genet 12: 1329–36PubMedCrossRefGoogle Scholar
  117. Oberdoerffer P, Sinclair DA (2007) The role of nuclear architecture in genomic instability and ageing. Nat Rev Mol Cell Biol 8: 692–702PubMedCrossRefGoogle Scholar
  118. Ottaviani A, Gilson E, Magdinier F (2008) Telomeric position effect: From the yeast paradigm to human pathologies? Biochimie 90: 93–107PubMedCrossRefGoogle Scholar
  119. Park SK, Prolla TA (2005) Gene expression profiling studies of aging in cardiac and skeletal muscles. Cardiovasc Res 66: 205–12PubMedCrossRefGoogle Scholar
  120. Pedram M, Sprung CN, Gao Q, Lo AW, Reynolds GE, Murnane JP (2006) Telomere position effect and silencing of transgenes near telomeres in the mouse. Mol Cell Biol 26: 1865–78PubMedCrossRefGoogle Scholar
  121. Peng JC, Karpen GH (2008) Epigenetic regulation of heterochromatic DNA stability. Curr Opin Genet Dev 18: 204–11PubMedCrossRefGoogle Scholar
  122. Pifer J, Stephan RP, Lill-Elghanian DA, Le PT, Witte PL (2003) Role of stromal cells and their products in protecting young and aged B-lineage precursors from dexamethasone-induced apoptosis. Mech Ageing Dev 124: 207–18PubMedCrossRefGoogle Scholar
  123. Pisano S, Galati A, Cacchione S (2008) Telomeric nucleosomes: Forgotten players at chromosome ends. Cell Mol Life SciGoogle Scholar
  124. Pletcher SD, Macdonald SJ, Marguerie R, Certa U, Stearns SC, Goldstein DB, Partridge L (2002) Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster. Curr Biol 12: 712–23PubMedCrossRefGoogle Scholar
  125. Rabbitts TH, Forster A, Baer R, Hamlyn PH (1983) Transcription enhancer identified near the human C mu immunoglobulin heavy chain gene is unavailable to the translocated c-myc gene in a Burkitt lymphoma. Nature 306: 806–9PubMedCrossRefGoogle Scholar
  126. Renauld H, Aparicio OM, Zierath PD, Billington BL, Chhablani 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: 1133–45PubMedCrossRefGoogle Scholar
  127. Riethman HC, Xiang Z, Paul S, Morse E, Hu XL, Flint J, Chi HC, Grady DL, Moyzis RK (2001) Integration of telomere sequences with the draft human genome sequence. Nature 409: 948–51PubMedCrossRefGoogle Scholar
  128. Rine J, Herskowitz I (1987) Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. Genetics 116: 9–22PubMedGoogle Scholar
  129. Robyr D, Suka Y, Xenarios I, Kurdistani SK, Wang A, Suka N, Grunstein M (2002) Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases. Cell 109: 437–46PubMedCrossRefGoogle Scholar
  130. Rogakou EP, Boon C, Redon C, Bonner WM (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146: 905–16PubMedCrossRefGoogle Scholar
  131. Rossi DJ, Bryder D, Zahn JM, Ahlenius H, Sonu R, Wagers AJ, Weissman IL (2005) Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci USA 102: 9194–9PubMedCrossRefGoogle Scholar
  132. Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, DePinho RA (1999) Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96: 701–12PubMedCrossRefGoogle Scholar
  133. Sarg B, Koutzamani E, Helliger W, Rundquist I, Lindner HH (2002) Postsynthetic trimethylation of histone H4 at lysine 20 in mammalian tissues is associated with aging. J Biol Chem 277: 39195–201PubMedCrossRefGoogle Scholar
  134. Scaffidi P, Misteli T (2006) Lamin A-dependent nuclear defects in human aging. Science 312: 1059–63PubMedCrossRefGoogle Scholar
  135. Scaffidi P, Misteli T (2008) Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol 10: 452–9PubMedCrossRefGoogle Scholar
  136. Schnabl B, Purbeck CA, Choi YH, Hagedorn CH, Brenner D (2003) Replicative senescence of activated human hepatic stellate cells is accompanied by a pronounced inflammatory but less fibrogenic phenotype. Hepatology 37: 653–64PubMedCrossRefGoogle Scholar
  137. Schoeftner S, Blasco MA (2008) Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10: 228–36PubMedCrossRefGoogle Scholar
  138. Sharma GG, Hwang KK, Pandita RK, Gupta A, Dhar S, Parenteau J, Agarwal M, Worman HJ, Wellinger RJ, Pandita TK (2003) Human heterochromatin protein 1 isoforms HP1(Hsalpha) and HP1(Hsbeta) interfere with hTERT-telomere interactions and correlate with changes in cell growth and response to ionizing radiation. Mol Cell Biol 23: 8363–76PubMedCrossRefGoogle Scholar
  139. Sharp A, Robinson D, Jacobs P (2000) Age- and tissue-specific variation of X chromosome inactivation ratios in normal women. Hum Genet 107: 343–9PubMedCrossRefGoogle Scholar
  140. Sharp JA, Fouts ET, Krawitz DC, Kaufman PD (2001) Yeast histone deposition protein Asf1p requires Hir proteins and PCNA for heterochromatic silencing. Curr Biol 11: 463–73PubMedCrossRefGoogle Scholar
  141. Shcheprova Z, Baldi S, Frei SB, Gonnet G, Barral Y (2008) A mechanism for asymmetric segregation of age during yeast budding. Nature 454: 728–34PubMedGoogle Scholar
  142. Shen S, Liu A, Li J, Wolubah C, Casaccia-Bonnefil P (2008) Epigenetic memory loss in aging oligodendrocytes in the corpus callosum. Neurobiol Aging 29: 452–63PubMedCrossRefGoogle Scholar
  143. Sinclair DA, Guarente L (1997) Extrachromosomal rDNA circles – a cause of aging in yeast. Cell 91: 1033–42PubMedCrossRefGoogle Scholar
  144. Singer MS, Kahana A, Wolf AJ, Meisinger LL, Peterson SE, Goggin C, Mahowald M, Gottschling DE (1998) Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae. Genetics 150: 613–32PubMedGoogle Scholar
  145. Sommer M, Poliak N, Upadhyay S, Ratovitski E, Nelkin BD, Donehower LA, Sidransky D (2006) DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell Cycle 5: 2005–11PubMedCrossRefGoogle Scholar
  146. Stephan RP, Lill-Elghanian DA, Witte PL (1997) Development of B cells in aged mice: decline in the ability of pro-B cells to respond to IL-7 but not to other growth factors. J Immunol 158: 1598–609PubMedGoogle Scholar
  147. Stone EM, Pillus L (1996) Activation of an MAP kinase cascade leads to Sir3p hyperphosphorylation and strengthens transcriptional silencing. J Cell Biol 135: 571–83PubMedCrossRefGoogle Scholar
  148. Taddei A, Gasser SM (2004) Multiple pathways for telomere tethering: functional implications of subnuclear position for heterochromatin formation. Biochim Biophys Acta 1677: 120–8PubMedGoogle Scholar
  149. Teixeira MT, Gilson E (2005) Telomere maintenance, function and evolution: the yeast paradigm. Chromosome Res 13: 535–48PubMedCrossRefGoogle Scholar
  150. Tham WH, Wyithe JS, Ferrigno PK, Silver PA, Zakian VA (2001) Localization of yeast telomeres to the nuclear periphery is separable from transcriptional repression and telomere stability functions. Mol Cell 8: 189–99PubMedCrossRefGoogle Scholar
  151. Trojer P, Reinberg D (2007) Facultative heterochromatin: is there a distinctive molecular signature? Mol Cell 28: 1–13PubMedCrossRefGoogle Scholar
  152. Valdes AM, Andrew T, Gardner JP, Kimura M, Oelsner E, Cherkas LF, Aviv A, Spector TD (2005) Obesity, cigarette smoking, and telomere length in women. Lancet 366: 662–4PubMedCrossRefGoogle Scholar
  153. Valenzuela L, Kamakaka RT (2006) Chromatin insulators. Annu Rev Genet 40: 107–38PubMedCrossRefGoogle Scholar
  154. Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D (2004) Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol Cell 16: 93–105PubMedCrossRefGoogle Scholar
  155. Wright WE, Shay JW (2002) Historical claims and current interpretations of replicative aging. Nat Biotechnol 20: 682–8PubMedCrossRefGoogle Scholar
  156. Ye X, Zerlanko B, Kennedy A, Banumathy G, Zhang R, Adams PD (2007) Downregulation of Wnt signaling is a trigger for formation of facultative heterochromatin and onset of cell senescence in primary human cells. Mol Cell 27: 183–96PubMedCrossRefGoogle Scholar
  157. Zhang H, Pan KH, Cohen SN (2003) Senescence-specific gene expression fingerprints reveal cell-type-dependent physical clustering of up-regulated chromosomal loci. Proc Natl Acad Sci USA 100: 3251–6PubMedCrossRefGoogle Scholar
  158. Zhang R, Adams PD (2007) Heterochromatin and its relationship to cell senescence and cancer therapy. Cell Cycle 6: 784–9PubMedCrossRefGoogle Scholar
  159. Zhang R, Chen W, Adams PD (2007) Molecular dissection of formation of senescence-associated heterochromatin foci. Mol Cell Biol 27: 2343–58PubMedCrossRefGoogle Scholar
  160. Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD (2005) Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell 8: 19–30PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, UCBL1, IFR128. 46 allée d’ItalieLyon Cedex 07France

Personalised recommendations