Chromatin Structure in Senescent Cells

  • Hunter W. Richards
  • Estela E. Medrano


The new millennium brought multiple discoveries of epigenetic events regulating the chromatin structure of normal and cancerous cells. Such renewed enthusiasm for chromatin studies was prompted by the development of new technologies and novel ideas that helped discover the “histone code.” It is now clear that posttranslational modifications of histone tails and insertion of histone variants regulate the structure of chromatin and, consequently, the fate of a cell during development, stem cell function, and cancer. Here, we review how the “emerging field of epigenetics in aging” has progressed, since it was found more than 30 years ago that old cells display decreased histone acetylation and increased reorganization of heterochromatin. We focus our discussion on structural changes of chromatin, the role of histone modifications and their modifiers, and highlight some paradigms and controversies regarding the opposite roles of class 1 and class 3 histone deacetylases in cellular senescence and tissue aging. We propose that an ever deregulated chromatin structure results in feed forward mechanisms of aberrant, tissue-specific gene expression and aging. Finally, we discuss how some drugs or hormones that target pathways regulated by histone modifiers can ameliorate some age-related dysfunctions.


Senescent Cell Histone Mark Replicative Senescence H3K9 Methylation Constitutive Heterochromatin 
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.



The Medrano laboratory is supported by National Institutes of Health grants (RO1 AG032135 and 2R01 CA84282) and a Senior Scholar Award from the Ellison Medical Foundation. HWR was supported by NIH training grant T32AG000183 We apologize for any omission but space limitations have prevented us to reference a large number of original papers and reviews.


  1. Abdelmohsen K, Pullmann R Jr, Lal A, Kim HH, Galban S, Yang X, Blethrow JD, Walker M, Shubert J, Gillespie DA, Furneaux H, Gorospe M (2007) Phosphorylation of HuR by Chk2 regulates SIRT1 expression. Mol Cell 25:543–557PubMedGoogle Scholar
  2. Allis CD, Wiggins JC (1984) Proteolytic processing of micronuclear H3 and histone phosphorylation during conjugation in Tetrahymena thermophila. Exp Cell Res 153:287–298PubMedGoogle Scholar
  3. Alvarez JD, Yasui DH, Niida H, Joh T, Loh DY, Kohwi-Shigematsu T (2000) The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev 14:521–535PubMedGoogle Scholar
  4. Arents G, Burlingame RW, Wang BC, Love WE, Moudrianakis EN (1991) The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assembly and a left-handed superhelix. Proc Natl Acad Sci USA 88:10148–10152PubMedGoogle Scholar
  5. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, Mostoslavsky R, Alt FW, Schibler U (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134:317–328PubMedGoogle Scholar
  6. Ausio J (2000) Are linker histones (histone H1) dispensable for survival? Bioessays 22:873–877PubMedGoogle Scholar
  7. Ayoub N, Jeyasekharan AD, Bernal JA, Venkitaraman AR (2008) HP1-beta mobilization promotes chromatin changes that initiate the DNA damage response. Nature 453:682–686PubMedGoogle Scholar
  8. Backs J, Olson EN (2006) Control of cardiac growth by histone acetylation/deacetylation. Circ Res 98:15–24PubMedGoogle Scholar
  9. Bakkenist CJ, Drissi R, Wu J, Kastan MB, Dome JS (2004) Disappearance of the telomere dysfunction-induced stress response in fully senescent cells. Cancer Res 64:3748–3752PubMedGoogle Scholar
  10. Bandyopadhyay D, Curry JL, Lin Q, Richards HW, Chen D, Hornsby PJ, Timchenko NA, Medrano EE (2007) Dynamic assembly of chromatin complexes during cellular senescence: implications for the growth arrest of human melanocytic nevi. Aging Cell 6:577–591PubMedGoogle Scholar
  11. Bandyopadhyay D, Medrano EE (2003) The emerging role of epigenetics in cellular and organismal aging. Exp Gerontol 38:1299–1307PubMedGoogle Scholar
  12. Bandyopadhyay D, Mishra A, Medrano EE (2004) Overexpression of histone deacetylase 1 confers resistance to sodium butyrate-mediated apoptosis in melanoma cells through a p53-mediated pathway. Cancer Res 64:7706–7710PubMedGoogle Scholar
  13. Bandyopadhyay D, Okan NA, Bales E, Nascimento L, Cole PA, Medrano EE (2002) Down-regulation of p300/CBP histone acetyltransferase activates a senescence checkpoint in human melanocytes. Cancer Res 62:6231–6239PubMedGoogle Scholar
  14. Bannister AJ, Schneider R, Kouzarides T (2002) Histone methylation: dynamic or static? Cell 109:801–806PubMedGoogle Scholar
  15. Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410:120–124PubMedGoogle Scholar
  16. Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA (2008) A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE 3:e2264PubMedGoogle Scholar
  17. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837PubMedGoogle Scholar
  18. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le CD, Shaw RJ, Navas P, Puigserver P, Ingram DK, de CR, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342PubMedGoogle Scholar
  19. Baxevanis AD, Arents G, Moudrianakis EN, Landsman D (1995) A variety of DNA-binding and multimeric proteins contain the histone fold motif. Nucleic Acids Res 23:2685–2691PubMedGoogle Scholar
  20. Baxter CS, Byvoet P (1975) CMR studies of protein modification. Progressive decrease in charge density at the epsilon-amino function of lysine with increasing methyl substitution. Biochem Biophys Res Commun 64:514–518PubMedGoogle Scholar
  21. Bernardi R, Pandolfi PP (2007) Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies. Nat Rev Mol Cell Biol 8:1006–1016PubMedGoogle Scholar
  22. Bertram MJ, Berube NG, Hang-Swanson X, Ran Q, Leung JK, Bryce S, Spurgers K, Bick RJ, Baldini A, Ning Y, Clark LJ, Parkinson EK, Barrett JC, Smith JR, Pereira-Smith OM (1999) Identification of a gene that reverses the immortal phenotype of a subset of cells and is a member of a novel family of transcription factor-like genes. Mol Cell Biol 19:1479–1485PubMedGoogle Scholar
  23. Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M (1999) A mammalian protein with specific demethylase activity for mCpG DNA. Nature 397:579–583PubMedGoogle Scholar
  24. Binda O, Nassif C, Branton PE (2008) SIRT1 negatively regulates HDAC1-dependent transcriptional repression by the RBP1 family of proteins. Oncogene 27:3384–3392PubMedGoogle Scholar
  25. Blasco MA (2007) The epigenetic regulation of mammalian telomeres. Nat Rev Genet 8:299–309PubMedGoogle Scholar
  26. Bordone L, Cohen D, Robinson A, Motta MC, van VE, Czopik A, Steele AD, Crowe H, Marmor S, Luo J, Gu W, Guarente L (2007) SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6:759–767PubMedGoogle Scholar
  27. Borek D, Otwinowski Z (2008) Kinetic control of eukaryotic chromatin structure by recursive topological restraints. Nature Precedings.
  28. Borra MT, Smith BC, Denu JM (2005) Mechanism of human SIRT1 activation by resveratrol. J Biol Chem 280:17187–17195Google Scholar
  29. Boyle AP, Davis S, Shulha HP, Meltzer P, Margulies EH, Weng Z, Furey TS, Crawford GE (2008) High-resolution mapping and characterization of open chromatin across the genome. Cell 132:311–322PubMedGoogle Scholar
  30. Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA (2007) Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 317:807–810PubMedGoogle Scholar
  31. Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Monch K, Minucci S, Porse BT, Marine JC, Hansen KH, Helin K (2007) The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 21:525–530PubMedGoogle Scholar
  32. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H, Dorken B, Jenuwein T, Schmitt CA (2005) Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436:660–665PubMedGoogle Scholar
  33. Brand M, Yamamoto K, Staub A, Tora L (1999) Identification of TATA-binding protein-free TAFII-containing complex subunits suggests a role in nucleosome acetylation and signal transduction. J Biol Chem 274:18285–18289PubMedGoogle Scholar
  34. Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T (1998) Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391:597–601PubMedGoogle Scholar
  35. Bringold F, Serrano M (2000) Tumor suppressors and oncogenes in cellular senescence. Exp Gerontol 35:317–329PubMedGoogle Scholar
  36. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303:2011–2015PubMedGoogle Scholar
  37. Bystricky K, Heun P, Gehlen L, Langowski J, Gasser SM (2004) Long-range compaction and flexibility of interphase chromatin in budding yeast analyzed by high-resolution imaging techniques. Proc Natl Acad Sci USA 101:16495–16500PubMedGoogle Scholar
  38. Cai S, Han HJ, Kohwi-Shigematsu T (2003) Tissue-specific nuclear architecture and gene expression regulated by SATB1. Nat Genet 34:42–51PubMedGoogle Scholar
  39. Cai S, Lee CC, Kohwi-Shigematsu T (2006) SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes. Nat Genet 38:1278–1288PubMedGoogle Scholar
  40. Carter DB, Chae CB (1975) Composition of liver histones in aging rat and mouse. J Gerontol 30:28–32PubMedGoogle Scholar
  41. Cattanach BM (1974) Position effect variegation in the mouse. Genet Res 23:291–306PubMedGoogle Scholar
  42. Chadwick BP, Willard HF (2001) A novel chromatin protein, distantly related to histone H2A, is largely excluded from the inactive X chromosome. J Cell Biol 152:375–384PubMedGoogle Scholar
  43. 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:e201Google Scholar
  44. Chan HM, Narita M, Lowe SW, Livingston DM (2005) The p400 E1A-associated protein is a novel component of the p53 –> p21 senescence pathway. Genes Dev 19:196–201PubMedGoogle Scholar
  45. Changolkar LN, Costanzi C, Leu NA, Chen D, McLaughlin KJ, Pehrson JR (2007) Developmental changes in histone macroH2A1-mediated gene regulation. Mol Cell Biol 27:2758–2764PubMedGoogle Scholar
  46. Changolkar LN, Pehrson JR (2006) macroH2A1 histone variants are depleted on active genes but concentrated on the inactive X chromosome. Mol Cell Biol 26:4410–4420PubMedGoogle Scholar
  47. Chen CC, Carson JJ, Feser J, Tamburini B, Zabaronick S, Linger J, Tyler JK (2008) Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair. Cell 134:231–243PubMedGoogle Scholar
  48. Chinenov Y (2002) A second catalytic domain in the Elp3 histone acetyltransferases: a candidate for histone demethylase activity? Trends Biochem Sci 27:115–117PubMedGoogle Scholar
  49. Clark KL, Halay ED, Lai E, Burley SK (1993) Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature 364:412–420PubMedGoogle Scholar
  50. Cloos PA, Christensen J, Agger K, Helin K (2008) Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev 22:1115–1140PubMedGoogle Scholar
  51. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760–764PubMedGoogle Scholar
  52. Cooper HM, Spelbrink JN (2008) The human SIRT3 protein deacetylase is exclusively mitochondrial. Biochem J 411:279–285PubMedGoogle Scholar
  53. Costanzi C, Pehrson JR (1998) Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature 393:599–601PubMedGoogle Scholar
  54. Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, Schneider R, Gregory PD, Tempst P, Bannister AJ, Kouzarides T (2004) Histone deimination antagonizes arginine methylation. Cell 118:545–553PubMedGoogle Scholar
  55. d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von ZT, Saretzki G, Carter NP, Jackson SP (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426:194–198PubMedGoogle Scholar
  56. Daujat S, Zeissler U, Waldmann T, Happel N, Schneider R (2005) HP1 binds specifically to Lys26-methylated histone H1.4, whereas simultaneous Ser27 phosphorylation blocks HP1 binding. J Biol Chem 280:38090–38095PubMedGoogle Scholar
  57. Davey CA, Sargent DF, Luger K, Maeder AW, Richmond TJ (2002) Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution. J Mol Biol 319:1097–1113PubMedGoogle Scholar
  58. De Koning L, Corpet A, Haber JE, Almouzni G (2007) Histone chaperones: an escort network regulating histone traffic. Nat Struct Mol Biol 14:997–1007PubMedGoogle Scholar
  59. de Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19:2100–2110PubMedGoogle Scholar
  60. de Wit E, Braunschweig U, Greil F, Bussemaker HJ, van SB (2008) Global chromatin domain organization of the Drosophila genome. PLoS Genet 4:e1000045PubMedGoogle Scholar
  61. Dechat T, Pfleghaar K, Sengupta K, Shimi T, Shumaker DK, Solimando L, Goldman RD (2008) Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22:832–853PubMedGoogle Scholar
  62. Dell’Orco RT, Worthington MI (1991) Histone H2A variant synthesis in aging human diploid cells. J Gerontol 46:B81–B83PubMedGoogle Scholar
  63. Deterding LJ, Bunger MK, Banks GC, Tomer KB, Archer TK (2008) Global changes in and characterization of specific sites of phosphorylation in mouse and human histone H1 Isoforms upon CDK inhibitor treatment using mass spectrometry. J Proteome Res 7:2368–2379PubMedGoogle Scholar
  64. Drabent B, Saftig P, Bode C, Doenecke D (2000) Spermatogenesis proceeds normally in mice without linker histone H1t. Histochem Cell Biol 113:433–442PubMedGoogle Scholar
  65. Duncan EM, Muratore-Schroeder TL, Cook RG, Garcia BA, Shabanowitz J, Hunt DF, Allis CD (2008) Cathepsin L proteolytically processes histone H3 during mouse embryonic stem cell differentiation. Cell 135:284–294PubMedGoogle Scholar
  66. Eissenberg JC (2001) Molecular biology of the chromo domain: an ancient chromatin module comes of age. Gene 275:19–29PubMedGoogle Scholar
  67. Eissenberg JC, Elgin SC (2000) The HP1 protein family: getting a grip on chromatin. Curr Opin Genet Dev 10:204–210PubMedGoogle Scholar
  68. Elliott PJ, Jirousek M (2008) Sirtuins: novel targets for metabolic disease. Curr Opin Investig Drugs 9:371–378PubMedGoogle Scholar
  69. Eot-Houllier G, Fulcrand G, Watanabe Y, Magnaghi-Jaulin L, Jaulin C (2008) Histone deacetylase 3 is required for centromeric H3K4 deacetylation and sister chromatid cohesion. Genes Dev 22:2639–2644PubMedGoogle Scholar
  70. Fan Y, Nikitina T, Morin-Kensicki EM, Zhao J, Magnuson TR, Woodcock CL, Skoultchi AI (2003) H1 linker histones are essential for mouse development and affect nucleosome spacing in vivo. Mol Cell Biol 23:4559–4572PubMedGoogle Scholar
  71. Fan Y, Nikitina T, Zhao J, Fleury TJ, Bhattacharyya R, Bouhassira EE, Stein A, Woodcock CL, Skoultchi AI (2005) Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell 123:1199–1212PubMedGoogle Scholar
  72. Fan Y, Sirotkin A, Russell RG, Ayala J, Skoultchi AI (2001) Individual somatic H1 subtypes are dispensable for mouse development even in mice lacking the H1(0) replacement subtype. Mol Cell Biol 21:7933–7943PubMedGoogle Scholar
  73. Feige JN, Lagouge M, Canto C, Strehle A, Houten SM, Milne JC, Lambert PD, Mataki C, Elliott PJ, Auwerx J (2008) Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab 8:347–358PubMedGoogle Scholar
  74. Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C, Lowe SW (2000) PML is induced by oncogenic ras and promotes premature senescence. Genes Dev 14:2015–2027PubMedGoogle Scholar
  75. Finkel T, Serrano M, Blasco MA (2007) The common biology of cancer and ageing. Nature 448:767–774PubMedGoogle Scholar
  76. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH (2007) Recovery of learning and memory is associated with chromatin remodelling. Nature 447:178–182PubMedGoogle Scholar
  77. Fraga MF, Agrelo R, Esteller M (2007) Cross-talk between aging and cancer: the epigenetic language. Ann N Y Acad Sci 1100:60–74PubMedGoogle Scholar
  78. Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23:413–418PubMedGoogle Scholar
  79. Frankel S, Rogina B (2005) Drosophila longevity is not affected by heterochromatin-mediated gene silencing. Aging Cell 4:53–56PubMedGoogle Scholar
  80. Frescas D, Guardavaccaro D, Bassermann F, Koyama-Nasu R, Pagano M (2007) JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes. Nature 450:309–313PubMedGoogle Scholar
  81. Frojdo S, Cozzone D, Vidal H, Pirola L (2007) Resveratrol is a class IA phosphoinositide 3-kinase inhibitor. Biochem J 406:511–518PubMedGoogle Scholar
  82. Funayama R, Saito M, Tanobe H, Ishikawa F (2006) Loss of linker histone H1 in cellular senescence. J Cell Biol 175:869–880PubMedGoogle Scholar
  83. Gan L, Mucke L (2008) Paths of convergence: sirtuins in aging and neurodegeneration. Neuron 58:10–14PubMedGoogle Scholar
  84. Gao L, Cueto MA, Asselbergs F, Atadja P (2002) Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem 277:25748–25755PubMedGoogle Scholar
  85. Garcia BA, Busby SA, Barber CM, Shabanowitz J, Allis CD, Hunt DF (2004) Characterization of phosphorylation sites on histone H1 isoforms by tandem mass spectrometry. J Proteome Res 3:1219–1227PubMedGoogle Scholar
  86. Garcia BA, Hake SB, Diaz RL, Kauer M, Morris SA, Recht J, Shabanowitz J, Mishra N, Strahl BD, Allis CD, Hunt DF (2007) Organismal differences in post-translational modifications in histones H3 and H4. J Biol Chem 282:7641–7655PubMedGoogle Scholar
  87. Garcia SN, Pereira-Smith O (2008) MRGing chromatin dynamics and cellular senescence. Cell Biochem Biophys 50:133–141PubMedGoogle Scholar
  88. Garcia-Cao M, Gonzalo S, Dean D, Blasco MA (2002) A role for the Rb family of proteins in controlling telomere length. Nat Genet 32:415–419PubMedGoogle Scholar
  89. 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 36:94–99PubMedGoogle Scholar
  90. Gardian G, Browne SE, Choi DK, Klivenyi P, Gregorio J, Kubilus JK, Ryu H, Langley B, Ratan RR, Ferrante RJ, Beal MF (2005) Neuroprotective effects of phenylbutyrate in the N171–82Q transgenic mouse model of Huntington’s disease. J Biol Chem 280:556–563PubMedGoogle Scholar
  91. Gariano RF, Gardner TW (2005) Retinal angiogenesis in development and disease. Nature 438:960–966PubMedGoogle Scholar
  92. Gaubatz JW, Cutler RG (1990) Mouse satellite DNA is transcribed in senescent cardiac muscle. J Biol Chem 265:17753–17758PubMedGoogle Scholar
  93. Geserick C, Blasco MA (2006) Novel roles for telomerase in aging. Mech Ageing Dev 127:579–583PubMedGoogle Scholar
  94. Gevry N, Chan HM, Laflamme L, Livingston DM, Gaudreau L (2007) p21 transcription is regulated by differential localization of histone H2A.Z. Genes Dev 21:1869–1881PubMedGoogle Scholar
  95. Glozak MA, Sengupta N, Zhang X, Seto E (2005) Acetylation and deacetylation of non-histone proteins. Gene 363:15–23PubMedGoogle Scholar
  96. Goldman MA (1988) The chromatin domain as a unit of gene regulation. Bioessays 9:50–55PubMedGoogle Scholar
  97. Goldman MA, Holmquist GP, Gray MC, Caston LA, Nag A (1984) Replication timing of genes and middle repetitive sequences. Science 224:686–692PubMedGoogle Scholar
  98. Gonzalo S, Blasco MA (2005) Role of Rb family in the epigenetic definition of chromatin. Cell Cycle 4:752–755PubMedGoogle Scholar
  99. 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 7:420–428PubMedGoogle Scholar
  100. Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Lobrich M, Jeggo PA (2008) ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell 31:167–177PubMedGoogle Scholar
  101. Grandinetti KB, David G (2008) Sin3B: an essential regulator of chromatin modifications at E2F target promoters during cell cycle withdrawal. Cell Cycle 7:1550–1554PubMedGoogle Scholar
  102. Guarente L (2008) Mitochondria–a nexus for aging, calorie restriction, and sirtuins? Cell 132:171–176PubMedGoogle Scholar
  103. Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, Eussen BH, de KA, Wessels L, de LW, van SB (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453:948–951PubMedGoogle Scholar
  104. Guillemette B, Gaudreau L (2006) Reuniting the contrasting functions of H2A.Z. Biochem Cell Biol 84:528–535PubMedGoogle Scholar
  105. Gupta A, Guerin-Peyrou TG, Sharma GG, Park C, Agarwal M, Ganju RK, Pandita S, Choi K, Sukumar S, Pandita RK, Ludwig T, Pandita TK (2008) The mammalian ortholog of Drosophila MOF that acetylates histone H4 lysine 16 is essential for embryogenesis and oncogenesis. Mol Cell Biol 28:397–409PubMedGoogle Scholar
  106. Haithcock E, Dayani Y, Neufeld E, Zahand AJ, Feinstein N, Mattout A, Gruenbaum Y, Liu J (2005) Age-related changes of nuclear architecture in Caenorhabditis elegans. Proc Natl Acad Sci USA 102:16690–16695PubMedGoogle Scholar
  107. Hake SB, Allis CD (2006) Histone H3 variants and their potential role in indexing mammalian genomes: the “H3 barcode hypothesis”. Proc Natl Acad Sci USA 103:6428–6435PubMedGoogle Scholar
  108. Hake SB, Garcia BA, Duncan EM, Kauer M, Dellaire G, Shabanowitz J, Bazett-Jones DP, Allis CD, Hunt DF (2006) Expression patterns and post-translational modifications associated with mammalian histone H3 variants. J Biol Chem 281:559–568PubMedGoogle Scholar
  109. Hale TK, Contreras A, Morrison AJ, Herrera RE (2006) Phosphorylation of the linker histone H1 by CDK regulates its binding to HP1alpha. Mol Cell 22:693–699PubMedGoogle Scholar
  110. Happel N, Doenecke D, Sekeri-Pataryas KE, Sourlingas TG (2008) H1 histone subtype constitution and phosphorylation state of the ageing cell system of human peripheral blood lymphocytes. Exp Gerontol 43:184–199PubMedGoogle Scholar
  111. Harbour JW, Dean DC (2000) Rb function in cell-cycle regulation and apoptosis. Nat Cell Biol 2:E65–E67PubMedGoogle Scholar
  112. Hediger F, Gasser SM (2006) Heterochromatin protein 1: don’t judge the book by its cover!. Curr Opin Genet Dev 16:143–150PubMedGoogle Scholar
  113. Heitz E (1928) Das Heterochromatin de Moose. Jahrb Wiss Botanik 69:762–818Google Scholar
  114. Hellauer K, Sirard E, Turcotte B (2001) Decreased expression of specific genes in yeast cells lacking histone H1. J Biol Chem 276:13587–13592PubMedGoogle Scholar
  115. Hendzel MJ, Lever MA, Crawford E, Th’ng JP (2004) The C-terminal domain is the primary determinant of histone H1 binding to chromatin in vivo. J Biol Chem 279:20028–20034PubMedGoogle Scholar
  116. Henikoff S, Furuyama T, Ahmad K (2004) Histone variants, nucleosome assembly and epigenetic inheritance. Trends Genet 20:320–326PubMedGoogle Scholar
  117. Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM (2006) Cellular senescence in aging primates. Science 311:1257PubMedGoogle Scholar
  118. Herrera RE, Nordheim A, Stewart AF (1997) Chromatin structure analysis of the human c-fos promoter reveals a centrally positioned nucleosome. Chromosoma 106:284–292PubMedGoogle Scholar
  119. Hill CS, Rimmer JM, Green BN, Finch JT, Thomas JO (1991) Histone-DNA interactions and their modulation by phosphorylation of -Ser-Pro-X-Lys/Arg- motifs. EMBO J 10:1939–1948PubMedGoogle Scholar
  120. Holmquist GP, Ashley T (2006) Chromosome organization and chromatin modification: influence on genome function and evolution. Cytogenet Genome Res 114:96–125PubMedGoogle Scholar
  121. Houde M, Shmookler Reis RJ, Goldstein S (1989) Proportions of H1 histone subspecies in human fibroblasts shift during density-dependent growth arrest independent of replicative senescence. Exp Cell Res 184:256–261PubMedGoogle Scholar
  122. Howard BH (1996) Replicative senescence: considerations relating to the stability of heterochromatin domains. Exp Gerontol 31:281–293PubMedGoogle Scholar
  123. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191–196PubMedGoogle Scholar
  124. Huang S, Risques RA, Martin GM, Rabinovitch PS, Oshima J (2008) Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A. Exp Cell Res 314:82–91PubMedGoogle Scholar
  125. Iakova P, Awad SS, Timchenko NA (2003) Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest. Cell 113:495–506PubMedGoogle Scholar
  126. Imai S, Armstrong CM, Kaeberlein M, Guarente L (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403:795–800PubMedGoogle Scholar
  127. Imai S, Kitano H (1998) Heterochromatin islands and their dynamic reorganization: a hypothesis for three distinctive features of cellular aging. Exp Gerontol 33:555–570PubMedGoogle Scholar
  128. Inoue Y, Kitagawa M, Taya Y (2007) Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F–1 after DNA damage. EMBO J 26:2083–2093PubMedGoogle Scholar
  129. Jacobs SA, Khorasanizadeh S (2002) Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science 295:2080–2083PubMedGoogle Scholar
  130. Jacobs SA, Taverna SD, Zhang Y, Briggs SD, Li J, Eissenberg JC, Allis CD, Khorasanizadeh S (2001) Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. EMBO J 20:5232–5241PubMedGoogle Scholar
  131. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl):245–254PubMedGoogle Scholar
  132. James TC, Elgin SC (1986) Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene. Mol Cell Biol 6:3862–3872PubMedGoogle Scholar
  133. Janicki SM, Tsukamoto T, Salghetti SE, Tansey WP, Sachidanandam R, Prasanth KV, Ried T, Shav-Tal Y, Bertrand E, Singer RH, Spector DL (2004) From silencing to gene expression: real-time analysis in single cells. Cell 116:683–698PubMedGoogle Scholar
  134. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080PubMedGoogle Scholar
  135. Jost JP (1993) Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine. Proc Natl Acad Sci USA 90:4684–4688PubMedGoogle Scholar
  136. Jost JP, Siegmann M, Sun L, Leung R (1995) Mechanisms of DNA demethylation in chicken embryos. Purification and properties of a 5-methylcytosine-DNA glycosylase. J Biol Chem 270:9734–9739PubMedGoogle Scholar
  137. Jost JP, Fremont M, Siegmann M, Hofsteenge J (1997) The RNA moiety of chick embryo 5-methylcytosine- DNA glycosylase targets DNA demethylation. Nucleic Acids Res 25:4545–4550PubMedGoogle Scholar
  138. Juan LJ, Utley RT, Adams CC, Vettese-Dadey M, Workman JL (1994) Differential repression of transcription factor binding by histone H1 is regulated by the core histone amino termini. EMBO J 13:6031–6040PubMedGoogle Scholar
  139. Juan LJ, Utley RT, Vignali M, Bohm L, Workman JL (1997) H1-mediated repression of transcription factor binding to a stably positioned nucleosome. J Biol Chem 272:3635–3640PubMedGoogle Scholar
  140. Juan LJ, Walter PP, Taylor IC, Kingston RE, Workman JL (1993) Nucleosome cores and histone H1 in the binding of GAL4 derivatives and the reactivation of transcription from nucleosome templates in vitro. Cold Spring Harb Symp Quant Biol 58:213–223PubMedGoogle Scholar
  141. Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, Bedalov A, Kennedy BK (2005) Substrate-specific activation of sirtuins by resveratrol. J Biol Chem 280:17038–17045Google Scholar
  142. Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570–2580PubMedGoogle Scholar
  143. Kaelin WG Jr (1999) Functions of the retinoblastoma protein. Bioessays 21:950–958PubMedGoogle Scholar
  144. Kang H, Cui K, Zhao K (2004) BRG1 controls the activity of the retinoblastoma protein via regulation of p21CIP1/WAF1/SDI. Mol Cell Biol 24:1188–1199PubMedGoogle Scholar
  145. Kang HL, Benzer S, Min KT (2002) Life extension in Drosophila by feeding a drug. Proc Natl Acad Sci USA 99:838–843PubMedGoogle Scholar
  146. Katan-Khaykovich Y, Struhl K (2005) Heterochromatin formation involves changes in histone modifications over multiple cell generations. EMBO J 24:2138–2149PubMedGoogle Scholar
  147. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH (2007a) SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J 26:3169–3179PubMedGoogle Scholar
  148. Kim EJ, Kho JH, Kang MR, Um SJ (2007b) Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity. Mol Cell 28:277–290PubMedGoogle Scholar
  149. Kim J, Daniel J, Espejo A, Lake A, Krishna M, Xia L, Zhang Y, Bedford MT (2006) Tudor, MBT and chromo domains gauge the degree of lysine methylation. EMBO Rep 7:397–403PubMedGoogle Scholar
  150. Kim MS, Kwon HJ, Lee YM, Baek JH, Jang JE, Lee SW, Moon EJ, Kim HS, Lee SK, Chung HY, Kim CW, Kim KW (2001) Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med 7:437–443PubMedGoogle Scholar
  151. Kim S, Benguria A, Lai CY, Jazwinski SM (1999) Modulation of life-span by histone deacetylase genes in Saccharomyces cerevisiae. Mol Biol Cell 10:3125–3136PubMedGoogle Scholar
  152. Kim S, Benoiton L, Paik WK (1964) Epsilon-alkyllysinase purification and properties of the enzyme. J Biol Chem 239:3790–3796PubMedGoogle Scholar
  153. Klose RJ, Zhang Y (2007) Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol 8:307–318PubMedGoogle Scholar
  154. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705PubMedGoogle Scholar
  155. Kurdistani SK (2007) Histone modifications as markers of cancer prognosis: a cellular view. Br J Cancer 97:1–5PubMedGoogle Scholar
  156. Kuriyan J, Eisenberg D (2007) The origin of protein interactions and allostery in colocalization. Nature 450:983–990PubMedGoogle Scholar
  157. Kuzmichev A, Jenuwein T, Tempst P, Reinberg D (2004) Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3. Mol Cell 14:183–193PubMedGoogle Scholar
  158. Lachner M, O’Carroll D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410:116–120PubMedGoogle Scholar
  159. Laible G, Haynes AR, Lebersorger A, O’Carroll D, Mattei MG, Denny P, Brown SD, Jenuwein T (1999) The murine polycomb-group genes Ezh1 and Ezh2 map close to Hox gene clusters on mouse chromosomes 11 and 6. Mamm Genome 10:311–314PubMedGoogle Scholar
  160. Lain S, Hollick JJ, Campbell J, Staples OD, Higgins M, Aoubala M, McCarthy A, Appleyard V, Murray KE, Baker L, Thompson A, Mathers J, Holland SJ, Stark MJ, Pass G, Woods J, Lane DP, Westwood NJ (2008) Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell 13:454–463PubMedGoogle Scholar
  161. Langan TA, Gautier J, Lohka M, Hollingsworth R, Moreno S, Nurse P, Maller J, Sclafani RA (1989) Mammalian growth-associated H1 histone kinase: a homolog of cdc2+/CDC28 protein kinases controlling mitotic entry in yeast and frog cells. Mol Cell Biol 9:3860–3868PubMedGoogle Scholar
  162. Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T (2002) Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21:2383–2396PubMedGoogle Scholar
  163. Latham JA, Dent SY (2007) Cross-regulation of histone modifications. Nat Struct Mol Biol 14:1017–1024PubMedGoogle Scholar
  164. Lavelle C, Prunell A (2007) Chromatin polymorphism and the nucleosome superfamily: a genealogy. Cell Cycle 6:2113–2119PubMedGoogle Scholar
  165. Lee CT, Duerre JA (1974) Changes in histone methylase activity of rat brain and liver with ageing. Nature 251:240–242PubMedGoogle Scholar
  166. Lee JS, Shilatifard A (2007) A site to remember: H3K36 methylation a mark for histone deacetylation. Mutat Res 618:130–134PubMedGoogle Scholar
  167. Li HL, Liu C, De CG, Ouzounian M, Sun M, Wang AB, Huang Y, He CW, Shi Y, Chen X, Nghiem MP, Liu Y, Chen M, Dawood F, Fukuoka M, Maekawa Y, Zhang L, Leask A, Ghosh AK, Kirshenbaum LA, Liu PP (2008a) Curcumin prevents and reverses murine cardiac hypertrophy. J Clin Invest 118:879–893PubMedGoogle Scholar
  168. Li Q, Xiao H, Isobe K (2002) Histone acetyltransferase activities of cAMP-regulated enhancer-binding protein and p300 in tissues of fetal, young, and old mice. J Gerontol A Biol Sci Med Sci 57:B93–B98PubMedGoogle Scholar
  169. Li Y, Xu W, McBurney MW, Longo VD (2008b) SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons. Cell Metab 8:38–48PubMedGoogle Scholar
  170. li-Youcef N, Lagouge M, Froelich S, Koehl C, Schoonjans K, Auwerx J (2007) Sirtuins: the ‘magnificent seven’, function, metabolism and longevity. Ann Med 39:335–345Google Scholar
  171. Lima-de-Faria A, Jaworska H (1968) Late DNA synthesis in heterochromatin. Nature 217:138–142PubMedGoogle Scholar
  172. Lin Q, Sirotkin A, Skoultchi AI (2000) Normal spermatogenesis in mice lacking the testis-specific linker histone H1t. Mol Cell Biol 20:2122–2128PubMedGoogle Scholar
  173. Lin R, Cook RG, Allis CD (1991) Proteolytic removal of core histone amino termini and dephosphorylation of histone H1 correlate with the formation of condensed chromatin and transcriptional silencing during Tetrahymena macronuclear development. Genes Dev 5:1601–1610PubMedGoogle Scholar
  174. Lindner H, Sarg B, Grunicke H, Helliger W (1999) Age-dependent deamidation of H1(0) histones in chromatin of mammalian tissues. J Cancer Res Clin Oncol 125:182–186PubMedGoogle Scholar
  175. Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen J, Malide D, Rovira II, Schimel D, Kuo CJ, Gutkind JS, Hwang PM, Finkel T (2007) Augmented Wnt signaling in a mammalian model of accelerated aging. Science 317:803–806PubMedGoogle Scholar
  176. Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV Jr, Weissman S, Verdin E, Schwer B (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 27:8807–8814PubMedGoogle Scholar
  177. Lomberk G, Bensi D, Fernandez-Zapico ME, Urrutia R (2006a) Evidence for the existence of an HP1-mediated subcode within the histone code. Nat Cell Biol 8:407–415PubMedGoogle Scholar
  178. Lomberk G, Wallrath L, Urrutia R (2006b) The heterochromatin protein 1 family. Genome Biol 7:228PubMedGoogle Scholar
  179. Luk E, Vu ND, Patteson K, Mizuguchi G, Wu WH, Ranjan A, Backus J, Sen S, Lewis M, Bai Y, Wu C (2007) Chz1, a nuclear chaperone for histone H2AZ. Mol Cell 25:357–368PubMedGoogle Scholar
  180. Macieira-Coelho A (1980) Implications of the reorganization of the cell genome for aging or immortalization of dividing cells in vitro. Gerontology 26:276–282PubMedGoogle Scholar
  181. Macieira-Coelho A, Puvion-Dutilleul F (1989) Evaluation of the reorganization in the high-order structure of DNA occurring during cell senescence. Mutat Res 219:165–170PubMedGoogle Scholar
  182. Macieiro-Coelho A (1984) Genome reorganization during cellular senescence. Mech Ageing Dev 27:257–262Google Scholar
  183. Macieiro-Coelho A (1991) Chromatin reorganization during senescence of proliferating cells. Mutat Res 256:81–104Google Scholar
  184. Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D, Harel-Bellan A (1998) Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature 391:601–605PubMedGoogle Scholar
  185. Malik HS, Henikoff S (2003) Phylogenomics of the nucleosome. Nat Struct Biol 10:882–891PubMedGoogle Scholar
  186. Mannervik M, Levine M (1999) The Rpd3 histone deacetylase is required for segmentation of the Drosophila embryo. Proc Natl Acad Sci USA 96:6797–6801PubMedGoogle Scholar
  187. Martin C, Zhang Y (2005) The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 6:838–849PubMedGoogle Scholar
  188. Matsumoto A (2002) Age-related changes in nuclear receptor coactivator immunoreactivity in motoneurons of the spinal nucleus of the bulbocavernosus of male rats. Brain Res 943:202–205PubMedGoogle Scholar
  189. McCarroll RM, Fangman WL (1988) Time of replication of yeast centromeres and telomeres. Cell 54:505–513PubMedGoogle Scholar
  190. McClintock D, Ratner D, Lokuge M, Owens DM, Gordon LB, Collins FS, Djabali K (2007) The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS ONE 2:e1269PubMedGoogle Scholar
  191. McGarvey KM, Van NL, Cope L, Ohm JE, Herman JG, Van CW, Schuebel KE, Baylin SB (2008) Defining a chromatin pattern that characterizes DNA-hypermethylated genes in colon cancer cells. Cancer Res 68:5753–5759PubMedGoogle Scholar
  192. Medvedev ZA, Medvedeva MN, Huschtscha LI (1977) Age changes of the pattern of F1 histone subfractions in rat liver and spleen chromatin. Gerontology 23:334–341PubMedGoogle Scholar
  193. Mehta IS, Figgitt M, Clements CS, Kill IR, Bridger JM (2007) Alterations to nuclear architecture and genome behavior in senescent cells. Ann N Y Acad Sci 1100:250–263PubMedGoogle Scholar
  194. Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM, Majoor DM, Shay JW, Mooi WJ, Peeper DS (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436:720–724PubMedGoogle Scholar
  195. Michan S, Sinclair D (2007) Sirtuins in mammals: insights into their biological function. Biochem J 404:1–13PubMedGoogle Scholar
  196. 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 452:492–496PubMedGoogle Scholar
  197. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I (2005) Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 16:4623–4635PubMedGoogle Scholar
  198. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450:712–716PubMedGoogle Scholar
  199. Milne JC, Denu JM (2008) The Sirtuin family: therapeutic targets to treat diseases of aging. Curr Opin Chem Biol 12:11–17PubMedGoogle Scholar
  200. Minc E, Allory Y, Worman HJ, Courvalin JC, Buendia B (1999) Localization and phosphorylation of HP1 proteins during the cell cycle in mammalian cells. Chromosoma 108:220–234PubMedGoogle Scholar
  201. Mishra RN, Kanungo MS (1994) Alterations in histones of the liver and oviduct of Japanese quail during aging. Mol Biol Rep 20:15–18PubMedGoogle Scholar
  202. Mitsui Y, Sakagami H, Murota S, Yamada M (1980) Age-related decline in histone H1 fraction in human diploid fibroblast cultures. Exp Cell Res 126:289–298PubMedGoogle Scholar
  203. Montgomery RL, Davis CA, Potthoff MJ, Haberland M, Fielitz J, Qi X, Hill JA, Richardson JA, Olson EN (2007) Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev 21:1790–1802PubMedGoogle Scholar
  204. Morimoto T, Sunagawa Y, Kawamura T, Takaya T, Wada H, Nagasawa A, Komeda M, Fujita M, Shimatsu A, Kita T, Hasegawa K (2008) The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats. J Clin Invest 118:868–878PubMedGoogle Scholar
  205. 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 124:315–329PubMedGoogle Scholar
  206. Murayama A, Ohmori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, Oie S, Daitoku H, Okuwaki M, Nagata K, Fukamizu A, Kimura K, Shimizu T, Yanagisawa J (2008) Epigenetic control of rDNA loci in response to intracellular energy status. Cell 133:627–639PubMedGoogle Scholar
  207. Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D, Guarente LP, Sassone-Corsi P (2008) The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134:329–340PubMedGoogle Scholar
  208. Nakamura Y, Ogura M, Tanaka D, Inagaki N (2008) Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5. Biochem Biophys Res Commun 366:174–179PubMedGoogle Scholar
  209. Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI (2001) Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292:110–113PubMedGoogle Scholar
  210. Napolitano MA, Cipollaro M, Cascino A, Melone MA, Giordano A, Galderisi U (2007) Brg1 chromatin remodeling factor is involved in cell growth arrest, apoptosis and senescence of rat mesenchymal stem cells. J Cell Sci 120:2904–2911PubMedGoogle Scholar
  211. Narita M, 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 126:503–514PubMedGoogle Scholar
  212. Narita M, Nunez S, Heard E, Narita M, 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 113:703–716PubMedGoogle Scholar
  213. Nielsen SJ, Schneider R, Bauer UM, Bannister AJ, Morrison A, O’Carroll D, Firestein R, Cleary M, Jenuwein T, Herrera RE, Kouzarides T (2001) Rb targets histone H3 methylation and HP1 to promoters. Nature 412:561–565PubMedGoogle Scholar
  214. Oberdoerffer P, Sinclair DA (2007) The role of nuclear architecture in genomic instability and ageing. Nat Rev Mol Cell Biol 8:692–702PubMedGoogle Scholar
  215. Ogryzko VV, Hirai TH, Russanova VR, Barbie DA, Howard BH (1996) Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent. Mol Cell Biol 16:5210–5218PubMedGoogle Scholar
  216. Oliveira AM, Wood MA, McDonough CB, Abel T (2007) Transgenic mice expressing an inhibitory truncated form of p300 exhibit long-term memory deficits. Learn Mem 14:564–572PubMedGoogle Scholar
  217. Oruetxebarria I, Venturini F, Kekarainen T, Houweling A, Zuijderduijn LM, Mohd-Sarip A, Vries RG, Hoeben RC, Verrijzer CP (2004) P16INK4a is required for hSNF5 chromatin remodeler-induced cellular senescence in malignant rhabdoid tumor cells. J Biol Chem 279:3807–3816PubMedGoogle Scholar
  218. Paik WK, Kim S (1973) Enzymatic demethylation of calf thymus histones. Biochem Biophys Res Commun 51:781–788PubMedGoogle Scholar
  219. Patterton HG, Landel CC, Landsman D, Peterson CL, Simpson RT (1998) The biochemical and phenotypic characterization of Hho1p, the putative linker histone H1 of Saccharomyces cerevisiae. J Biol Chem 273:7268–7276PubMedGoogle Scholar
  220. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le CD, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de CR (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8:157–168PubMedGoogle Scholar
  221. Pehrson JR, Costanzi C, Dharia C (1997) Developmental and tissue expression patterns of histone macroH2A1 subtypes. J Cell Biochem 65:107–113PubMedGoogle Scholar
  222. Pehrson JR, Fuji RN (1998) Evolutionary conservation of histone macroH2A subtypes and domains. Nucleic Acids Res 26:2837–2842PubMedGoogle Scholar
  223. Pena AN, Pereira-Smith OM (2007) The role of the MORF/MRG family of genes in cell growth, differentiation, DNA repair, and thereby aging. Ann N Y Acad Sci 1100:299–305PubMedGoogle Scholar
  224. Pennings S, Meersseman G, Bradbury EM (1994) Linker histones H1 and H5 prevent the mobility of positioned nucleosomes. Proc Natl Acad Sci USA 91:10275–10279PubMedGoogle Scholar
  225. Perumalswami P, Kleiner DE, Lutchman G, Heller T, Borg B, Park Y, Liang TJ, Hoofnagle JH, Ghany MG (2006) Steatosis and progression of fibrosis in untreated patients with chronic hepatitis C infection. Hepatology 43:780–787PubMedGoogle Scholar
  226. Peters AH, Kubicek S, Mechtler K, O’Sullivan RJ, Derijck AA, Perez-Burgos L, Kohlmaier A, Opravil S, Tachibana M, Shinkai Y, Martens JH, Jenuwein T (2003) Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell 12:1577–1589PubMedGoogle Scholar
  227. Peters AH, O’Carroll D, Scherthan H, Mechtler K, Sauer S, Schofer C, Weipoltshammer K, Pagani M, Lachner M, Kohlmaier A, Opravil S, Doyle M, Sibilia M, Jenuwein T (2001) Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107:323–337PubMedGoogle Scholar
  228. Pfau R, Tzatsos A, Kampranis SC, Serebrennikova OB, Bear SE, Tsichlis PN (2008) Members of a family of JmjC domain-containing oncoproteins immortalize embryonic fibroblasts via a JmjC domain-dependent process. Proc Natl Acad Sci USA 105:1907–1912PubMedGoogle Scholar
  229. Pickersgill H, Kalverda B, de WE, Talhout W, Fornerod M, van SB (2006) Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat Genet 38:1005–1014PubMedGoogle Scholar
  230. Pina B, Martinez P, Suau P (1988) Differential acetylation of core histones in rat cerebral cortex neurons during development and aging. Eur J Biochem 174:311–315PubMedGoogle Scholar
  231. Pina B, Suau P (1987) Changes in histones H2A and H3 variant composition in differentiating and mature rat brain cortical neurons. Dev Biol 123:51–58PubMedGoogle Scholar
  232. Polo SE, Almouzni G (2006) Chromatin assembly: a basic recipe with various flavours. Curr Opin Genet Dev 16:104–111PubMedGoogle Scholar
  233. Prashad N, Cutler RG (1976) Percent satellite DNA as a function of tissue and age of mice. Biochim Biophys Acta 418:1–23PubMedGoogle Scholar
  234. Puvion-Dutilleul F, Macieira-Coelho A (1983) Aging dependent nucleolar and chromatin changes in cultivated fibroblasts. Cell Biol Int Rep 7:61–71PubMedGoogle Scholar
  235. Puvion-Dutilleul F, Macieiro-Coelho A (1982) Ultrastructural organization of nucleoproteins during aging of cultured human embryonic fibroblasts. Exp Cell Res 138:423–429PubMedGoogle Scholar
  236. Qiu Y, Zhao Y, Becker M, John S, Parekh BS, Huang S, Hendarwanto A, Martinez ED, Chen Y, Lu H, Adkins NL, Stavreva DA, Wiench M, Georgel PT, Schiltz RL, Hager GL (2006) HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription. Mol Cell 22:669–679PubMedGoogle Scholar
  237. Rabini S, Franke K, Saftig P, Bode C, Doenecke D, Drabent B (2000) Spermatogenesis in mice is not affected by histone H1.1 deficiency. Exp Cell Res 255:114–124PubMedGoogle Scholar
  238. Ramon A, Muro-Pastor MI, Scazzocchio C, Gonzalez R (2000) Deletion of the unique gene encoding a typical histone H1 has no apparent phenotype in Aspergillus nidulans. Mol Microbiol 35:223–233PubMedGoogle Scholar
  239. Rastogi S, Joshi B, Dasgupta P, Morris M, Wright K, Chellappan S (2006) Prohibitin facilitates cellular senescence by recruiting specific corepressors to inhibit E2F target genes. Mol Cell Biol 26:4161–4171PubMedGoogle Scholar
  240. Rea S, Eisenhaber F, O’Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD, Jenuwein T (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406:593–599PubMedGoogle Scholar
  241. Redon C, Pilch D, Rogakou E, Sedelnikova O, Newrock K, Bonner W (2002) Histone H2A variants H2AX and H2AZ. Curr Opin Genet Dev 12:162–169PubMedGoogle Scholar
  242. Richards HW, Hale TK, Marx JM, Herrera RE, Medrano EE (2008): Unpublished WorkGoogle Scholar
  243. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273:5858–5868PubMedGoogle Scholar
  244. Rogakou EP, Sekeri-Pataryas KE (1999) Histone variants of H2A and H3 families are regulated during in vitro aging in the same manner as during differentiation. Exp Gerontol 34:741–754PubMedGoogle Scholar
  245. Rogina B, Helfand SL, Frankel S (2002) Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction. Science 298:1745PubMedGoogle Scholar
  246. Roth SY, Allis CD (1992) Chromatin condensation: does histone H1 dephosphorylation play a role? Trends Biochem Sci 17:93–98PubMedGoogle Scholar
  247. Ryan JM, Cristofalo VJ (1972) Histone acetylation during aging of human cells in culture. Biochem Biophys Res Commun 48:735–742PubMedGoogle Scholar
  248. Sapojnikova N, Thorne A, Myers F, Staynov D, Crane-Robinson C (2009) The chromatin of active genes is not in a permanently open conformation. J Mol Biol 386:290–299PubMedGoogle Scholar
  249. Sarg B, Helliger W, Hoertnagl B, Puschendorf B, Lindner H (1999) The N-terminally acetylated form of mammalian histone H1(o), but not that of avian histone H5, increases with age. Arch Biochem Biophys 372:333–339PubMedGoogle Scholar
  250. 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 277:39195–39201PubMedGoogle Scholar
  251. Sasaki T, Maier B, Bartke A, Scrable H (2006) Progressive loss of SIRT1 with cell cycle withdrawal. Aging Cell 5:413–422PubMedGoogle Scholar
  252. Scher MB, Vaquero A, Reinberg D (2007) SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev 21:920–928PubMedGoogle Scholar
  253. Schneider J, Shilatifard A (2006) Histone demethylation by hydroxylation: chemistry in action. ACS Chem Biol 1:75–81PubMedGoogle Scholar
  254. Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G, Reinberg D, Jenuwein T (2004) A silencing pathway to induce H3–K9 and H4–K20 trimethylation at constitutive heterochromatin. Genes Dev 18:1251–1262PubMedGoogle Scholar
  255. Schwer B, Verdin E (2008) Conserved metabolic regulatory functions of sirtuins. Cell Metab 7:104–112PubMedGoogle Scholar
  256. Sedelnikova OA, Horikawa I, Zimonjic DB, Popescu NC, Bonner WM, Barrett JC (2004) Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat Cell Biol 6:168–170PubMedGoogle Scholar
  257. Sedgwick B (2004) Repairing DNA-methylation damage. Nat Rev Mol Cell Biol 5:148–157PubMedGoogle Scholar
  258. Sedivy JM, Banumathy G, Adams PD (2008) Aging by epigenetics-A consequence of chromatin damage? Exp Cell Res 314:1909–1917PubMedGoogle Scholar
  259. Seshadri T, Campisi J (1990) Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts. Science 247:205–209PubMedGoogle Scholar
  260. Shay JW, Wright WE (2005) Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis 26:867–874PubMedGoogle Scholar
  261. Shen X, Gorovsky MA (1996) Linker histone H1 regulates specific gene expression but not global transcription in vivo. Cell 86:475–483PubMedGoogle Scholar
  262. Shen X, Yu L, Weir JW, Gorovsky MA (1995) Linker histones are not essential and affect chromatin condensation in vivo. Cell 82:47–56PubMedGoogle Scholar
  263. Shi Y (2007) Histone lysine demethylases: emerging roles in development, physiology and disease. Nat Rev Genet 8:829–833PubMedGoogle Scholar
  264. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941–953PubMedGoogle Scholar
  265. Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, Eriksson M, Goldman AE, Khuon S, Collins FS, Jenuwein T, Goldman RD (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci USA 103:8703–8708PubMedGoogle Scholar
  266. Sims RJI, Reinberg D (2006) Histone H3 Lys 4 methylation: caught in a bind? Genes Dev 20:2779–2786PubMedGoogle Scholar
  267. Sirotkin AM, Edelmann W, Cheng G, Klein-Szanto A, Kucherlapati R, Skoultchi AI (1995) Mice develop normally without the H1(0) linker histone. Proc Natl Acad Sci USA 92:6434–6438PubMedGoogle Scholar
  268. Smallwood A, Esteve PO, Pradhan S, Carey M (2007) Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev 21:1169–1178PubMedGoogle Scholar
  269. Smith E, Shilatifard A (2007) The A, B, Gs of silencing. Genes Dev 21:1141–1144PubMedGoogle Scholar
  270. Smith JS, Costello JF (2006) A broad band of silence. Nat Genet 38:504–506PubMedGoogle Scholar
  271. Smothers JF, Henikoff S (2001) The hinge and chromo shadow domain impart distinct targeting of HP1-like proteins. Mol Cell Biol 21:2555–2569PubMedGoogle Scholar
  272. Southern EM (1970) Base sequence and evolution of guinea-pig alpha-satellite DNA. Nature 227:794–798PubMedGoogle Scholar
  273. Soutoglou E, Misteli T (2008) Activation of the cellular DNA damage response in the absence of DNA lesions. Science 320:1507–1510PubMedGoogle Scholar
  274. Stewart SA, Weinberg RA (2006) Telomeres: cancer to human aging. Annu Rev Cell Dev Biol 22:531–557PubMedGoogle Scholar
  275. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45PubMedGoogle Scholar
  276. Stunkel W, Kober I, Seifart KH (1997) A nucleosome positioned in the distal promoter region activates transcription of the human U6 gene. Mol Cell Biol 17:4397–4405PubMedGoogle Scholar
  277. Tagami H, Ray-Gallet D, Almouzni G, Nakatani Y (2004) Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 116:51–61PubMedGoogle Scholar
  278. Tajul-Arifin K, Teasdale R, Ravasi T, Hume DA, Mattick JS (2003) Identification and analysis of chromodomain-containing proteins encoded in the mouse transcriptome. Genome Res 13:1416–1429PubMedGoogle Scholar
  279. Talasz H, Helliger W, Puschendorf B, Lindner H (1996) In vivo phosphorylation of histone H1 variants during the cell cycle. Biochemistry 35:1761–1767PubMedGoogle Scholar
  280. Taverna SD, Li H, Ruthenburg AJ, Allis CD, Patel DJ (2007) How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol 14:1025–1040PubMedGoogle Scholar
  281. Ten Hagen KG, Gilbert DM, Willard HF, Cohen SN (1990) Replication timing of DNA sequences associated with human centromeres and telomeres. Mol Cell Biol 10:6348–6355PubMedGoogle Scholar
  282. Timchenko LT, Salisbury E, Wang GL, Nguyen H, Albrecht JH, Hershey JW, Timchenko NA (2006) Age-specific CUGBP1-eIF2 complex increases translation of CCAAT/enhancer-binding protein beta in old liver. J Biol Chem 281:32806–32819PubMedGoogle Scholar
  283. Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–230PubMedGoogle Scholar
  284. Tonini T, D’Andrilli G, Fucito A, Gaspa L, Bagella L (2008) Importance of Ezh2 polycomb protein in tumorigenesis process interfering with the pathway of growth suppressive key elements. J Cell Physiol 214:295–300PubMedGoogle Scholar
  285. Trojer P, Reinberg D (2007) Facultative heterochromatin: is there a distinctive molecular signature? Mol Cell 28:1–13PubMedGoogle Scholar
  286. Vakoc CR, Mandat SA, Olenchock BA, Blobel GA (2005) Histone H3 lysine 9 methylation and HP1gamma are associated with transcription elongation through mammalian chromatin. Mol Cell 19:381–391PubMedGoogle Scholar
  287. van der Heijden GW, Derijck AA, Posfai E, Giele M, Pelczar P, Ramos L, Wansink DG, van der Vlag J, Peters AH, de Boer P (2007) Chromosome-wide nucleosome replacement and H3.3 incorporation during mammalian meiotic sex chromosome inactivation. Nat Genet 39:251–258PubMedGoogle Scholar
  288. van der Heijden GW, Ramos L, Baart EB, van den Berg IM, Derijck AA, van der Vlag J, Martini E, de Boer P (2008) Sperm-derived histones contribute to zygotic chromatin in humans. BMC Dev Biol 8:34PubMedGoogle Scholar
  289. Van Holde KE (1989) Chromatin. Springer-Verlag, New YorkGoogle Scholar
  290. Vaquero A, Scher M, Erdjument-Bromage H, Tempst P, Serrano L, Reinberg D (2007) SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Nature 450:440–444PubMedGoogle Scholar
  291. 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 16:93–105PubMedGoogle Scholar
  292. Vaquero A, Scher MB, Lee DH, Sutton A, Cheng HL, Alt FW, Serrano L, Sternglanz R, Reinberg D (2006) SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev 20:1256–1261PubMedGoogle Scholar
  293. Vassetzky Y, Hair A, Mechali M (2000) Rearrangement of chromatin domains during development in Xenopus. Genes Dev 14:1541–1552PubMedGoogle Scholar
  294. Verdone L, Caserta M, Di ME (2005) Role of histone acetylation in the control of gene expression. Biochem Cell Biol 83:344–353PubMedGoogle Scholar
  295. Villeponteau B (1997) The heterochromatin loss model of aging. Exp Gerontol 32:383–394PubMedGoogle Scholar
  296. von Hahn HP (1964) Age-related alteration in the structure of DNA. II. The role of histones. Gerontologia. 10:174–182Google Scholar
  297. von Hahn HP, Miller J, Eichhorn GL (1969) Age-related alterations in the structure of nucleoprotein IV. Changes in the composition of whole histone from rat liver. Gerontologia 15:293–301Google Scholar
  298. Wagner AP, Iordachel MC, Wagner LP (1982) Age changes in the H1 group of histones from rat liver. Exp Gerontol 17:173–177PubMedGoogle Scholar
  299. Wallace JA, Orr-Weaver TL (2005) Replication of heterochromatin: insights into mechanisms of epigenetic inheritance. Chromosoma 114:389–402PubMedGoogle Scholar
  300. Walsh G, Jefferis R (2006) Post-translational modifications in the context of therapeutic proteins. Nat Biotechnol 24:1241–1252PubMedGoogle Scholar
  301. Wang AG, Seo SB, Moon HB, Shin HJ, Kim DH, Kim JM, Lee TH, Kwon HJ, Yu DY, Lee DS (2005) Hepatic steatosis in transgenic mice overexpressing human histone deacetylase 1. Biochem Biophys Res Commun 330:461–466PubMedGoogle Scholar
  302. Wang GG, Cai L, Pasillas MP, Kamps MP (2007a) NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat Cell Biol 9:804–812PubMedGoogle Scholar
  303. Wang GL, Salisbury E, Shi X, Timchenko L, Medrano EE, Timchenko NA (2008a) HDAC1 cooperates with C/EBPalpha in the inhibition of liver proliferation in old mice. J. Biol, ChemGoogle Scholar
  304. Wang GL, Salisbury E, Shi X, Timchenko L, Medrano EE, Timchenko NA (2008b) HDAC1 promotes liver proliferation in young mice via interactions with C/EBP beta. J. Biol, ChemGoogle Scholar
  305. Wang GL, Shi X, Salisbury E, Sun Y, Albrecht JH, Smith RG, Timchenko NA (2006) Cyclin D3 maintains growth-inhibitory activity of C/EBPalpha by stabilizing C/EBPalpha-cdk2 and C/EBPalpha-Brm complexes. Mol Cell Biol 26:2570–2582PubMedGoogle Scholar
  306. Wang GL, Shi X, Salisbury E, Sun Y, Albrecht JH, Smith RG, Timchenko NA (2007b) Growth hormone corrects proliferation and transcription of phosphoenolpyruvate carboxykinase in livers of old mice via elimination of CCAAT/enhancer-binding protein alpha-Brm complex. J Biol Chem 282:1468–1478PubMedGoogle Scholar
  307. Wareham KA, Lyon MF, Glenister PH, Williams ED (1987) Age related reactivation of an X-linked gene. Nature 327:725–727PubMedGoogle Scholar
  308. Weiss A, Keshet I, Razin A, Cedar H (1996) DNA demethylation in vitro: involvement of RNA. Cell 86:709–718PubMedGoogle Scholar
  309. Whetstine JR, Ceron J, Ladd B, Dufourcq P, Reinke V, Shi Y (2005) Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase. Mol Cell 18:483–490PubMedGoogle Scholar
  310. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686–689PubMedGoogle Scholar
  311. Woodcock CL, Skoultchi AI, Fan Y (2006) Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length. Chromosome Res 14:17–25PubMedGoogle Scholar
  312. Wu CH, van RJ, Yetil A, Fan AC, Bachireddy P, Felsher DW (2007) Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc Natl Acad Sci USA 104:13028–13033PubMedGoogle Scholar
  313. Wu P, de Lange T (2008) No overt nucleosome eviction at deprotected telomeres. Mol Cell Biol 28:5721–5735Google Scholar
  314. Yamaguchi M, Tonou-Fujimori N, Komori A, Maeda R, Nojima Y, Li H, Okamoto H, Masai I (2005) Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways. Development 132:3027–3043PubMedGoogle Scholar
  315. Yang XJ (2004) Lysine acetylation and the bromodomain: a new partnership for signaling. Bioessays 26:1076–1087PubMedGoogle Scholar
  316. Yang XJ, Seto E (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9:206–218PubMedGoogle Scholar
  317. 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 27:183–196PubMedGoogle Scholar
  318. Yuan GC, Liu YJ, Dion MF, Slack MD, Wu LF, Altschuler SJ, Rando OJ (2005) Genome-scale identification of nucleosome positions in S. cerevisiae. Science 309:626–630PubMedGoogle Scholar
  319. Yunis JJ, Yasmineh WG (1971) Heterochromatin, satellite DNA, and cell function. Science 174:1200–1209PubMedGoogle Scholar
  320. 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 100:3251–3256PubMedGoogle Scholar
  321. Zhang P, Du J, Sun B, Dong X, Xu G, Zhou J, Huang Q, Liu Q, Hao Q, Ding J (2006) Structure of human MRG15 chromo domain and its binding to Lys36-methylated histone H3. Nucleic Acids Res 34:6621–6628PubMedGoogle Scholar
  322. Zhang R, Adams PD (2007) Heterochromatin and its relationship to cell senescence and cancer therapy. Cell Cycle 6:784–789PubMedGoogle Scholar
  323. Zhang R, Chen W, Adams PD (2007) Molecular dissection of formation of senescence-associated heterochromatin foci. Mol Cell Biol 27:2343–2358PubMedGoogle Scholar
  324. 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 8:19–30PubMedGoogle Scholar
  325. Zhao W, Kruse JP, Tang Y, Jung SY, Qin J, Gu W (2008) Negative regulation of the deacetylase SIRT1 by DBC1. Nature 451:587–590PubMedGoogle Scholar
  326. Zhong S, Salomoni P, Pandolfi PP (2000) The transcriptional role of PML and the nuclear body. Nat Cell Biol 2:E85–E90PubMedGoogle Scholar
  327. Zupkovitz G, Tischler J, Posch M, Sadzak I, Ramsauer K, Egger G, Grausenburger R, Schweifer N, Chiocca S, Decker T, Seiser C (2006) Negative and positive regulation of gene expression by mouse histone deacetylase 1. Mol Cell Biol 26:7913–7928PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonUSA

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