Cell Biochemistry and Biophysics

, Volume 50, Issue 3, pp 133–141 | Cite as

MRGing Chromatin Dynamics and Cellular Senescence

Review Paper

Abstract

Normal primary cells have a finite ability to divide in culture and after a number of population doublings enter a state of irreversible cell cycle arrest known as replicative senescence. Several cellular stresses have been shown to induce a senescence-like growth arrest including shortened telomeres, DNA-damaging stresses, and drastic changes in chromatin structure, for example, through histone deacetylase (HDAC) induction. Histones are core components of chromatin which are subject to a number of chemical modifications that influence the dynamic state of chromatin structure. Proper chromatin structure formation is crucial for most DNA-dependent processes including transcription, replication, and repair which have a profound impact on cellular proliferation and senescence. Several genes important for chromatin remodeling such as the tumor suppressors p53 and retinoblastoma (Rb) affect cellular senescence by mediating changes in chromatin structure and gene expression. The Morf4-Related Gene (MRG) family of transcription factors forms stable interactions with chromatin-modifying complexes including histone acetyltransferase (HAT) and HDAC complexes and interact with Rb. Further, the MRG family was founded by a gene, Mortality Factor on Chromosome 4, capable of inducing senescence in immortalized cell lines. In this paper, we review the role of the MRG family of proteins in chromatin dynamics and cellular senescence.

Keywords

NuA4 Sin3-HDAC1 Eaf3 DNA repair Aging 

References

  1. 1.
    Hayflick, L., & Moorhead, P. S. (1961). The serial cultivation of human diploid cell strains. Experimental Cell Research, 25, 585–621.Google Scholar
  2. 2.
    Hayflick, L. (1965). The limited in vitro lifetime of human diploid cell strains. Experimental Cell Research, 37, 614–636.PubMedGoogle Scholar
  3. 3.
    Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O. et al. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proceedings of the National Academy of Sciences of the United States of America, 92, 9363–9367.PubMedGoogle Scholar
  4. 4.
    Shelton, D. N., Chang, E., Whittier, P. S., Choi, D., & Funk, W. D. (1999). Microarray analysis of replicative senescence. Current Biology, 9, 939–945.PubMedGoogle Scholar
  5. 5.
    Campisi, J. (2001). Cellular senescence as a tumor-suppressor mechanism. Trends in Cell Biology, 11, S27–S31.PubMedGoogle Scholar
  6. 6.
    Narita, M., Nunez, S., Heard, E., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell, 113, 703–716.PubMedGoogle Scholar
  7. 7.
    Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguria, A., Zaballos, A., Flores, J. M., Barbacid, M., Beach, D., & Serrano, M. (2005). Tumour biology: Senescence in premalignant tumours. Nature, 436, 642.PubMedGoogle Scholar
  8. 8.
    Angello, J. C., Pendergrass, W. R., Norwood, T. H., & Prothero, J. (1989). Cell enlargement: One possible mechanism underlying cellular senescence. Journal of Cellular Physiology, 140, 288–294.PubMedGoogle Scholar
  9. 9.
    Ogryzko, V. V., Hirai, T. H., Russanova, V. R., Barbie, D. A., & Howard, B. H. (1996). Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent. Molecular and Cellular Biology, 16, 5210–5218.PubMedGoogle Scholar
  10. 10.
    Russanova, V. R., Hirai, T. H., & Howard, B. H. (2004). Semirandom sampling to detect differentiation-related and age-related epigenome remodeling. Journal of Gerontology Series A, Biology Sciences and Medical Sciences, 59, 1221–1233.Google Scholar
  11. 11.
    Russanova, V. R., Hirai, T. H., Tchernov, A. V., & Howard, B. H. (2004). Mapping development-related and age-related chromatin remodeling by a high throughput ChIP-HPLC approach. Journal of Gerontology Series A, Biology Sciences and Medical Sciences, 59, 1234–1243.Google Scholar
  12. 12.
    Sarg, B., Koutzamani, E., Helliger, W., Rundquist, I., & Lindner, H. H. (2002). Postsynthetic trimethylation of histone H4 at lysine 20 in mammalian tissues is associated with aging. Journal of Biological Chemistry, 277, 39195–39201.PubMedGoogle Scholar
  13. 13.
    Stewart, S. A., Ben-Porath, I., Carey, V. J., O’Connor, B. F., Hahn, W. C., & Weinberg, R. A. (2003). Erosion of the telomeric single-strand overhang at replicative senescence. Nature Genetics, 33, 492–496.PubMedGoogle Scholar
  14. 14.
    Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C. P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998). Extension of life-span by introduction of telomerase into normal human cells. Science, 279, 349–352.PubMedGoogle Scholar
  15. 15.
    van Steensel, B., Smogorzewska, A., & de Lange, T. (1998). TRF2 protects human telomeres from end-to-end fusions. Cell, 92, 401–413.PubMedGoogle Scholar
  16. 16.
    Atadja, P., Wong, H., Garkavtsev, I., Veillette, C., & Riabowol, K. (1995). Increased activity of p53 in senescing fibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 92, 8348–8352.PubMedGoogle Scholar
  17. 17.
    Vaziri, H., West, M. D., Allsopp, R. C., Davison, T. S., Wu, Y. S., Arrowsmith, C. H., Poirier, G. G., & Benchimol, S. (1997). ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase. EMBO Journal, 16, 6018–6033.PubMedGoogle Scholar
  18. 18.
    Jacobs, J. J., & de Lange, T. (2004). Significant role for p16INK4a in p53-independent telomere-directed senescence. Current Biology, 14, 2302–2308.PubMedGoogle Scholar
  19. 19.
    Davis, T., Singhrao, S. K., Wyllie, F. S., Haughton, M. F., Smith, P. J., Wiltshire, M., Wynford-Thomas, D., Jones, C. J., Faragher, R. G., & Kipling, D. (2003). Telomere-based proliferative lifespan barriers in Werner-syndrome fibroblasts involve both p53-dependent and p53-independent mechanisms. Journal of Cell Science, 116, 1349–1357.PubMedGoogle Scholar
  20. 20.
    Dickson, M. A., Hahn, W. C., Ino, Y., Ronfard, V., Wu, J. Y., Weinberg, R. A., Louis, D. N., Li, F. P., & Rheinwald, J. G. (2000). Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Molecular and Cellular Biology, 20, 1436–1447.PubMedGoogle Scholar
  21. 21.
    Rudolph, K. L., Chang, S., Lee, H. W., Blasco, M., Gottlieb, G. J., Greider, C., & DePinho, R. A. (1999). Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell, 96, 701–712.PubMedGoogle Scholar
  22. 22.
    O’Brien, W., Stenman, G., & Sager, R. (1986). Suppression of tumor growth by senescence in virally transformed human fibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 83, 8659–8663.PubMedGoogle Scholar
  23. 23.
    Pereira-Smith, O. M., & Smith, J. R. (1983). Evidence for the recessive nature of cellular immortality. Science, 221, 964–966.PubMedGoogle Scholar
  24. 24.
    Pereira-Smith, O. M., & Smith, J. R. (1988). Genetic analysis of indefinite division in human cells: identification of four complementation groups. Proceedings of the National Academy of Sciences of the United States of America, 85, 6042–6046.PubMedGoogle Scholar
  25. 25.
    Mallette, F. A., Gaumont-Leclerc, M. F., & Ferbeyre, G. (2007). The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence. Genes and Development, 21, 43–48.PubMedGoogle Scholar
  26. 26.
    Ning, Y., Weber, J. L., Killary, A. M., Ledbetter, D. H., Smith, J. R., & Pereira-Smith, O. M. (1991). Genetic analysis of indefinite division in human cells: evidence for a cell senescence-related gene(s) on human chromosome 4. Proceedings of the National Academy of Sciences of the United States of America, 88, 5635–5639.PubMedGoogle Scholar
  27. 27.
    Bertram, M. J., Berube, N. G., Hang-Swanson, X., Ran, Q., Leung, J. K., Bryce, S., Spurgers, K., Bick, R. J., Baldini, A., Ning, Y., Clark, L. J., Parkinson, E. K., Barrett, J. C., Smith, J. R., & Pereira-Smith, O. M. (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. Molecular and Cellular Biology, 19, 1479–1485.PubMedGoogle Scholar
  28. 28.
    Bertram, M. J., & Pereira-Smith, O. M. (2001). Conservation of the MORF4 related gene family: Identification of a new chromo domain subfamily and novel protein motif. Gene, 266, 111–121.PubMedGoogle Scholar
  29. 29.
    Khorasanizadeh, S. (2004). The nucleosome: From genomic organization to genomic regulation. Cell, 116, 259–272.PubMedGoogle Scholar
  30. 30.
    Strahl, B. D., & Allis, C. D. (2000). The language of covalent histone modifications. Nature, 403, 41–45.PubMedGoogle Scholar
  31. 31.
    Luger, K., & Richmond, T. J. (1998). The histone tails of the nucleosome. Current Opinion in Genetics and Development, 8, 140–146.PubMedGoogle Scholar
  32. 32.
    Kornberg, R. D., & Lorch, Y. (1999). Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell, 98, 285–294.PubMedGoogle Scholar
  33. 33.
    Marmorstein, R. (2004). Structural and chemical basis of histone acetylation. Novartis Foundation Symposium, 259, 78–98 discussion 98–101, 163–109.PubMedGoogle Scholar
  34. 34.
    Bannister, A. J., & Kouzarides, T. (2005). Reversing histone methylation. Nature, 436, 1103–1106.PubMedGoogle Scholar
  35. 35.
    Mai, A., Massa, S., Rotili, D., Cerbara, I., Valente, S., Pezzi, R., Simeoni, S., & Ragno, R. (2005). Histone deacetylation in epigenetics: An attractive target for anticancer therapy. Medicinal Research Reviews, 25, 261–309.PubMedGoogle Scholar
  36. 36.
    Wolffe, A. P., & Hayes, J. J. (1999). Chromatin disruption and modification. Nucleic Acids Research, 27, 711–720.PubMedGoogle Scholar
  37. 37.
    Hansen, J. C., Tse, C., & Wolffe, A. P. (1998). Structure and function of the core histone N-termini: More than meets the eye. Biochemistry, 37, 17637–17641.PubMedGoogle Scholar
  38. 38.
    Clark, D., Reitman, M., Studitsky, V., Chung, J., Westphal, H., Lee, E., & Felsenfeld, G. (1993). Chromatin structure of transcriptionally active genes. Cold Spring Harbor Symposia Quantitative Biology, 58, 1–6.Google Scholar
  39. 39.
    Tse, C., Fletcher, T. M., & Hansen, J. C. (1998). Enhanced transcription factor access to arrays of histone H3/H4 tetramer DNA complexes in vitro: Implications for replication and transcription. Proceedings of the National Academy of Sciences of the United States of America, 95, 12169–12173.PubMedGoogle Scholar
  40. 40.
    Grunstein, M. (1997). Histone acetylation in chromatin structure and transcription. Nature, 389, 349–352.PubMedGoogle Scholar
  41. 41.
    Clarke, A. S., Samal, E., & Pillus, L. (2006). Distinct roles for the essential MYST family HAT Esa1p in transcriptional silencing. Molecular Biology of the Cell, 17, 1744–1757.PubMedGoogle Scholar
  42. 42.
    Wang, Y., Fischle, W., Cheung, W., Jacobs, S., Khorasanizadeh, S., & Allis, C. D. (2004). Beyond the double helix: Writing and reading the histone code. Novartis Foundation Symposium, 259, 3–17 discussion 17–21, 163–169.PubMedGoogle Scholar
  43. 43.
    Grienenberger, A., Miotto, B., Sagnier, T., Cavalli, G., Schramke, V., Geli, V., Mariol, M. C., Berenger, H., Graba, Y., & Pradel, J. (2002). The MYST domain acetyltransferase Chameau functions in epigenetic mechanisms of transcriptional repression. Current Biology, 12, 762–766.PubMedGoogle Scholar
  44. 44.
    Deckert, J., & Struhl, K. (2001). Histone acetylation at promoters is differentially affected by specific activators and repressors. Molecular and Cellular Biology, 21, 2726–2735.PubMedGoogle Scholar
  45. 45.
    Lachner, M., & Jenuwein, T. (2002). The many faces of histone lysine methylation. Current Opinion in Cell Biology, 14, 286–298.PubMedGoogle Scholar
  46. 46.
    Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., & Zhang, Y. (2002). Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science, 298, 1039–1043.PubMedGoogle Scholar
  47. 47.
    Schneider, R., Bannister, A. J., Myers, F. A., Thorne, A. W., Crane-Robinson, C., & Kouzarides, T. (2004). Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nature Cell Biology, 6, 73–77.PubMedGoogle Scholar
  48. 48.
    Kobza, K., Camporeale, G., Rueckert, B., Kueh, A., Griffin, J. B., Sarath, G., & Zempleni, J. (2005). K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase. FEBS Journal, 272, 4249–4259.PubMedGoogle Scholar
  49. 49.
    Bauer, U. M., Daujat, S., Nielsen, S. J., Nightingale, K., & Kouzarides, T. (2002). Methylation at arginine 17 of histone H3 is linked to gene activation. EMBO Reports, 3, 39–44.PubMedGoogle Scholar
  50. 50.
    Boggs, B. A., Cheung, P., Heard, E., Spector, D. L., Chinault, A. C., & Allis, C. D. (2002). Differentially methylated forms of histone H3 show unique association patterns with inactive human X chromosomes. Nature Genetics, 30, 73–76.PubMedGoogle Scholar
  51. 51.
    Bannister, A. J., Zegerman, P., Partridge, J. F., Miska, E. A., Thomas, J. O., Allshire, R. C., & Kouzarides, T. (2001). Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature, 410, 120–124.PubMedGoogle Scholar
  52. 52.
    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, 116–120.PubMedGoogle Scholar
  53. 53.
    Chen, D., Ma, H., Hong, H., Koh, S. S., Huang, S. M., Schurter, B. T., Aswad, D. W., & Stallcup, M. R. (1999). Regulation of transcription by a protein methyltransferase. Science, 284, 2174–2177.PubMedGoogle Scholar
  54. 54.
    Bardeesy, N., & Sharpless, N. E. (2006). RAS unplugged: Negative feedback and oncogene-induced senescence. Cancer Cell, 10, 451–453.PubMedGoogle Scholar
  55. 55.
    Cox, L. S., & Faragher, R. G. (2007). From old organisms to new molecules: Integrative biology and therapeutic targets in accelerated human ageing. Cellular and Molecular Life Sciences, 64, 2620–2641.PubMedGoogle Scholar
  56. 56.
    Hornsby, P. J. (2002). Cellular senescence and tissue aging in vivo. Journal of Gerontology Series A, Biological Sciences and Medical Sciences, 57, B251–B256.Google Scholar
  57. 57.
    Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A. H., Schlegelberger, B., Stein, H., Dorken, B., Jenuwein, T., & Schmitt, C. A. (2005). Oncogene-induced senescence as an initial barrier in lymphoma development. Nature, 436, 660–665.PubMedGoogle Scholar
  58. 58.
    Gonzalo, S., Garcia-Cao, M., Fraga, M. F., Schotta, G., Peters, A. H., Cotter, S. E., Eguia, R., Dean, D. C., Esteller, M., Jenuwein, T., & Blasco, M. A. (2005). Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nature Cell Biology, 7, 420–428.PubMedGoogle Scholar
  59. 59.
    Zhang, R., Poustovoitov, M. V., Ye, X., Santos, H. A., Chen, W., Daganzo, S. M., Erzberger, J. P., Serebriiskii, I. G., Canutescu, A. A., Dunbrack, R. L., Pehrson, J. R., Berger, J. M., Kaufman, P. D., & Adams, P. D. (2005). Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Developmental Cell, 8, 19–30.PubMedGoogle Scholar
  60. 60.
    Narita, M., Krizhanovsky, V., Nunez, S., Chicas, A., Hearn, S. A., Myers, M. P., & Lowe, S. W. (2006). A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell, 126, 503–514.PubMedGoogle Scholar
  61. 61.
    Rogakou, E. P., & Sekeri-Pataryas, K. E. (1999). Histone variants of H2A and H3 families are regulated during in vitro aging in the same manner as during differentiation. Experimental Gerontology, 34, 741–754.PubMedGoogle Scholar
  62. 62.
    Narita, M. (2007). Cellular senescence and chromatin organisation. British Journal of Cancer, 96, 686–691.PubMedGoogle Scholar
  63. 63.
    Funayama, R., & Ishikawa, F. (2007). Cellular senescence and chromatin structure. Chromosoma, 116, 431–440.PubMedGoogle Scholar
  64. 64.
    Allis, C. D., Berger, S. L., Cote, J., Dent, S., Jenuwien, T., Kouzarides, T., Pillus, L., Reinberg, D., Shi, Y., Shiekhattar, R., Shilatifard, A., Workman, J., & Zhang, Y. (2007). New nomenclature for chromatin-modifying enzymes. Cell, 131, 633–636.PubMedGoogle Scholar
  65. 65.
    Wei, W., Herbig, U., Wei, S., Dutriaux, A., & Sedivy, J. M. (2003). Loss of retinoblastoma but not p16 function allows bypass of replicative senescence in human fibroblasts. EMBO Reports, 4, 1061–1066.PubMedGoogle Scholar
  66. 66.
    Zhang, R., Chen, W., & Adams, P. D. (2007). Molecular dissection of formation of senescence-associated heterochromatin foci. Molecular and Cellular Biology, 27, 2343–2358.PubMedGoogle Scholar
  67. 67.
    Bandyopadhyay, D., Curry, J. L., Lin, Q., Richards, H. W., Chen, D., Hornsby, P. J., Timchenko, N. A., & Medrano, E. E. (2007). Dynamic assembly of chromatin complexes during cellular senescence: Implications for the growth arrest of human melanocytic nevi. Aging Cell, 6, 577–591.PubMedGoogle Scholar
  68. 68.
    Sage, J., Mulligan, G. J., Attardi, L. D., Miller, A., Chen, S., Williams, B., Theodorou, E., & Jacks, T. (2000). Targeted disruption of the three Rb-related genes leads to loss of G(1) control and immortalization. Genes and Development, 14, 3037–3050.PubMedGoogle Scholar
  69. 69.
    Jackson, J. G., & Pereira-Smith, O. M. (2006). Primary and compensatory roles for RB family members at cell cycle gene promoters that are deacetylated and downregulated in doxorubicin-induced senescence of breast cancer cells. Molecular and Cellular Biology, 26, 2501–2510.PubMedGoogle Scholar
  70. 70.
    Zhang, P., Zhao, J., Wang, B., Du, J., Lu, Y., Chen, J., & Ding, J. (2006). The MRG domain of human MRG15 uses a shallow hydrophobic pocket to interact with the N-terminal region of PAM14. Protein Science, 15, 2423–2434.PubMedGoogle Scholar
  71. 71.
    Bowman, B. R., Moure, C. M., Kirtane, B. M., Welschhans, R. L., Tominaga, K., Pereira-Smith, O. M., & Quiocho, F. A. (2006). Multipurpose MRG domain involved in cell senescence and proliferation exhibits structural homology to a DNA-interacting domain. Structure, 14, 151–158.PubMedGoogle Scholar
  72. 72.
    Pardo, P. S., Leung, J. K., Lucchesi, J. C., & Pereira-Smith, O. M. (2002). MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation. Journal of Biological Chemistry, 277, 50860–50866.PubMedGoogle Scholar
  73. 73.
    Tominaga, K., Leung, J. K., Rookard, P., Echigo, J., Smith, J. R., & Pereira-Smith, O. M. (2003). MRGX is a novel transcriptional regulator that exhibits activation or repression of the B-myb promoter in a cell type-dependent manner. Journal of Biological Chemistry, 278, 49618–49624.PubMedGoogle Scholar
  74. 74.
    Tominaga, K., Kirtane, B., Jackson, J. G., Ikeno, Y., Ikeda, T., Hawks, C., Smith, J. R., Matzuk, M. M., & Pereira-Smith, O. M. (2005). MRG15 regulates embryonic development and cell proliferation. Molecular and Cellular Biology, 25, 2924–2937.PubMedGoogle Scholar
  75. 75.
    Marin, I., & Baker, B. S. (2000). Origin and evolution of the regulatory gene male-specific lethal-3. Molecular Biology and Evolution, 17, 1240–1250.PubMedGoogle Scholar
  76. 76.
    Kusch, T., Florens, L., Macdonald, W. H., Swanson, S. K., Glaser, R. L., Yates, J. R. III, Abmayr, S. M., Washburn, M. P., & Workman, J. L. (2004). Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science, 306, 2084–2087.PubMedGoogle Scholar
  77. 77.
    Eisen, A., Utley, R. T., Nourani, A., Allard, S., Schmidt, P., Lane, W. S., Lucchesi, J. C., & Cote, J. (2001). The yeast NuA4 and Drosophila MSL complexes contain homologous subunits important for transcription regulation. Journal of Biological Chemistry, 276, 3484–3491.PubMedGoogle Scholar
  78. 78.
    Koonin, E. V., Zhou, S., & Lucchesi, J. C. (1995). The chromo superfamily: New members, duplication of the chromo domain and possible role in delivering transcription regulators to chromatin. Nucleic Acids Research, 23, 4229–4233.PubMedGoogle Scholar
  79. 79.
    Tominaga, K., Matzuk, M. M., & Pereira-Smith, O. M. (2005). MrgX is not essential for cell growth and development in the mouse. Molecular and Cellular Biology, 25, 4873–4880.PubMedGoogle Scholar
  80. 80.
    Yochum, G. S., & Ayer, D. E. (2002). Role for the mortality factors MORF4, MRGX, and MRG15 in transcriptional repression via associations with Pf1, mSin3A, and transducin-like enhancer of split. Molecular and Cellular Biology, 22, 7868–7876.PubMedGoogle Scholar
  81. 81.
    Leung, J. K., Berube, N., Venable, S., Ahmed, S., Timchenko, N., & Pereira-Smith, O. M. (2001). MRG15 activates the B-myb promoter through formation of a nuclear complex with the retinoblastoma protein and the novel protein PAM14. Journal of Biological Chemistry, 276, 39171–39178.PubMedGoogle Scholar
  82. 82.
    Hayakawa, T., Ohtani, Y., Hayakawa, N., Shinmyozu, K., Saito, M., Ishikawa, F., & Nakayama, J. (2007). RBP2 is an MRG15 complex component and down-regulates intragenic histone H3 lysine 4 methylation. Genes Cells, 12, 811–826.PubMedGoogle Scholar
  83. 83.
    Olgun, A., Aleksenko, T., Pereira-Smith, O. M., & Vassilatis, D. K. (2005). Functional analysis of MRG-1: The ortholog of human MRG15 in Caenorhabditis elegans. Journal of Gerontology Series A, Biology Sciences and Medical Sciences, 60, 543–548.Google Scholar
  84. 84.
    Takasaki, T., Liu, Z., Habara, Y., Nishiwaki, K., Nakayama, J., Inoue, K., Sakamoto, H., & Strome, S. (2007). MRG-1, an autosome-associated protein, silences X-linked genes and protects germline immortality in Caenorhabditis elegans. Development, 134, 757–767.PubMedGoogle Scholar
  85. 85.
    Reid, J. L., Moqtaderi, Z., & Struhl, K. (2004). Eaf3 regulates the global pattern of histone acetylation in Saccharomyces cerevisiae. Molecular and Cellular Biology, 24, 757–764.PubMedGoogle Scholar
  86. 86.
    Carrozza, M. J., Li, B., Florens, L., Suganuma, T., Swanson, S. K., Lee, K. K., Shia, W. J., Anderson, S., Yates, J., Washburn, M. P., & Workman, J. L. (2005). Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell, 123, 581–592.PubMedGoogle Scholar
  87. 87.
    Joshi, A. A., & Struhl, K. (2005). Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Molecular Cell, 20, 971–978.PubMedGoogle Scholar
  88. 88.
    Li, B., Gogol, M., Carey, M., Lee, D., Seidel, C., & Workman, J. L. (2007). Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin. Science, 316, 1050–1054.PubMedGoogle Scholar
  89. 89.
    Keogh, M. C., Kurdistani, S. K., Morris, S. A., Ahn, S. H., Podolny, V., Collins, S. R., Schuldiner, M., Chin, K., Punna, T., Thompson, N. J., Boone, C., Emili, A., Weissman, J. S., Hughes, T. R., Strahl, B. D., Grunstein, M., Greenblatt, J. F., Buratowski, S., & Krogan, N. J. (2005). Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell, 123, 593–605.PubMedGoogle Scholar
  90. 90.
    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 Research, 34, 6621–6628.PubMedGoogle Scholar
  91. 91.
    Han, X., Berardi, P., & Riabowol, K. (2006). Chromatin modification and senescence: Linkage by tumor suppressors? Rejuvenation Research, 9, 69–76.PubMedGoogle Scholar
  92. 92.
    Doyon, Y., Selleck, W., Lane, W. S., Tan, S., & Cote, J. (2004). Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Molecular and Cellular Biology, 24, 1884–1896.PubMedGoogle Scholar
  93. 93.
    Cai, Y., Jin, J., Tomomori-Sato, C., Sato, S., Sorokina, I., Parmely, T. J., Conaway, R. C., & Conaway, J. W. (2003). Identification of new subunits of the multiprotein mammalian TRRAP/TIP60-containing histone acetyltransferase complex. Journal of Biological Chemistry, 278, 42733–42736.PubMedGoogle Scholar
  94. 94.
    Doyon, Y., & Cote, J. (2004). The highly conserved and multifunctional NuA4 HAT complex. Current Opinion in Genetics and Development, 14, 147–154.PubMedGoogle Scholar
  95. 95.
    Iakova, P., Awad, S. S., & Timchenko, N. A. (2003). Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest. Cell, 113, 495–506.PubMedGoogle Scholar
  96. 96.
    Dunaief, J. L., Strober, B. E., Guha, S., Khavari, P. A., Alin, K., Luban, J., Begemann, M., Crabtree, G. R., & Goff, S. P. (1994). The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell, 79, 119–130.PubMedGoogle Scholar
  97. 97.
    Shanahan, F., Seghezzi, W., Parry, D., Mahony, D., & Lees, E. (1999). Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest. Molecular and Cellular Biology, 19, 1460–1469.PubMedGoogle Scholar
  98. 98.
    Di Micco, R., Fumagalli, M., Cicalese, A., Piccinin, S., Gasparini, P., Luise, C., Schurra, C., Garre, M., Nuciforo, P. G., Bensimon, A., Maestro, R., Pelicci, P. G., & d’Adda di Fagagna, F. (2006). Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature, 444, 638–642.PubMedGoogle Scholar
  99. 99.
    Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L. V., Kolettas, E., Niforou, K., Zoumpourlis, V. C., Takaoka, M., Nakagawa, H., Tort, F., Fugger, K., Johansson, F., Sehested, M., Andersen, C. L., Dyrskjot, L., Orntoft, T., Lukas, J., Kittas, C., Helleday, T., Halazonetis, T. D., Bartek, J., & Gorgoulis, V. G. (2006). Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature, 444, 633–637.PubMedGoogle Scholar
  100. 100.
    Di Leonardo, A., Linke, S. P., Clarkin, K., & Wahl, G. M. (1994). DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes and Development, 8, 2540–2551.PubMedGoogle Scholar
  101. 101.
    Garcia, S. N., Kirtane, B. M., Podlutsky, A. J., Pereira-Smith, O. M., & Tominaga, K. (2007). Mrg15 null and heterozygous mouse embryonic fibroblasts exhibit DNA-repair defects post exposure to gamma ionizing radiation. FEBS Letters, 581, 5275–5281.PubMedGoogle Scholar
  102. 102.
    Downs, J. A., & Cote, J. (2005). Dynamics of chromatin during the repair of DNA double-strand breaks. Cell Cycle, 4, 1373–1376.PubMedGoogle Scholar
  103. 103.
    Bartek, J., Lukas, J., & Bartkova, J. (2007). DNA damage response as an anti-cancer barrier: damage threshold and the concept of ‘conditional haploinsufficiency’. Cell Cycle, 6, 2344–2347.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Department of Cellular and Structural Biology, STCBM 3.100The University of Texas Health Sciences Center at San AntonioSan AntonioUSA

Personalised recommendations