Epigenetics

Abstract

In the past, the term epigenetics was used to describe all biological phenomena that do not follow normal genetic rules. Currently, it is generally accepted that epigenetics refers to the heritable modifications of the genome that do not involve changes in the primary DNA sequence. Important epigenetic events include DNA methylation, covalent post-transcriptional histone modifications, RNA-mediated silencing, and nucleosome remodeling. These epigenetic inheritances take place in the chromatin-mediated control of gene expression and are responsible for chromatin structure stability, genome integrity, modulation of the expression of tissue-specific genes, and embryonic development, which are essential mechanisms allowing the stable propagation of gene activity states from one generation of cells to the next. Importantly, during the past years, epigenetic

events have emerged to be considered as key mechanisms in the regulation of critical biological processes and in the development of human diseases. From this point of view, the importance of epigenetic events in the control of both normal cellular processes and altered events associated with diseases has led to epigenetics being considered as a new frontier in cancer research.

Keywords

Histone Modification Imprint Gene Histone Tail Histone Code Lysine Acetylation 
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.

Abbreviations

CoA

coenzyme A

DNA

deoxyribonucleic acid

DNMT

DNA methyltransferase

ER

endoplasmic reticulum

FDA

Federal Drug Administration

HAT

histone acetyltransferase

HDAC

histone deacetylase

HDACi

histone deacetylase inhibitor

HMT

histone methyltransferase

ICR

imprinting control region

LOI

loss of imprinting

RNA

ribonucleic acid

TSA

test set accuracy

References

  1. 29.1.
    R. Taby, J.P. Issa: Cancer epigenetics, CA Cancer J. Clin. 60(6), 376–392 (2010)CrossRefGoogle Scholar
  2. 29.2.
    A. Portela, M. Esteller: Epigenetic modifications and human disease, Nat. Biotechnol. 28(10), 1057–1068 (2010)CrossRefGoogle Scholar
  3. 29.3.
    S. Winter, W. Fischle: Epigenetic markers and their cross-talk, Essay Biochem. 48(1), 45–61 (2010)CrossRefGoogle Scholar
  4. 29.4.
    P.A. Jones, S.B. Baylin: The fundamental role of epigenetic events in cancer, Nat. Rev. Genet. 3(6), 415–428 (2002)Google Scholar
  5. 29.5.
    P.A. Jones, S.B. Baylin: The epigenomics of cancer, Cell 128(4), 683–692 (2007)CrossRefGoogle Scholar
  6. 29.6.
    N. Avvakumov, A. Nourani, J. Côté: Histone chaperones: Modulators of chromatin marks, Mol. Cell 41(5), 502–514 (2011)CrossRefGoogle Scholar
  7. 29.7.
    C. Cinti, M. Macaluso, A. Giordano: Tumor-specific exon 1 mutations could be the `hit eventʼ predisposing Rb2/p130 gene to epigenetic silencing in lung cancer, Oncogene 24(38), 5821–5826 (2005)CrossRefGoogle Scholar
  8. 29.8.
    L. Bai, A.V. Morozov: Gene regulation by nucleosome positioning, Trends Genet. 26(11), 476–483 (2010)CrossRefGoogle Scholar
  9. 29.9.
    R. Jaenisch, A. Bird: Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals, Nat. Genet. 33, 245–254 (2003)CrossRefGoogle Scholar
  10. 29.10.
    T. Vaissièe, C. Sawan, Z. Herceg: Epigenetic interplay between histone modifications and DNA methylation in gene silencing, Mutat. Res. 659(1–2), 40–48 (2008)CrossRefGoogle Scholar
  11. 29.11.
    J.P. Thomson, P.J. Skene, J. Selfridge, T. Clouaire, J. Guy, S. Webb, A.R. Kerr, A. Deaton, R. Andrews, K.D. James, D.J. Turner, R. Illingworth, A. Bird: CpG islands influence chromatin structure via the CpG-binding protein Cfp1, Nature 464(7291), 1082–1086 (2010)CrossRefGoogle Scholar
  12. 29.12.
    C. Lanzuolo, V. Orlando: The function of the epigenome in cell reprogramming, Cell Mol. Life Sci. 64(9), 1043–1062 (2007)CrossRefGoogle Scholar
  13. 29.13.
    E.T. Liu: Functional genomics of cancer, Curr. Opin. Genet. Dev. 18(3), 251–256 (2008)CrossRefGoogle Scholar
  14. 29.14.
    D. Van Heemst, P.M. den Reijer, R.G. Westendorp: Ageing or cancer: A review on the role of caretakers and gatekeepers, Eur. J. Cancer 43(15), 2144–2152 (2007)CrossRefGoogle Scholar
  15. 29.15.
    A.P. Bird: CpG-rich islands and the function of DNA methylation, Nature 321(6067), 209–213 (1986)CrossRefGoogle Scholar
  16. 29.16.
    R.A. Hinshelwood, J.R. Melki, L.I. Huschtscha, C. Paul, J.Z. Song, C. Stirzaker, R.R. Reddel, S.J. Clark: Aberrant de novo methylation of the p16INK4A CpG island is initiated post gene silencing in association with chromatin remodelling and mimics nucleosome positioning, Hum. Mol. Genet. 18(16), 3098–3109 (2009)CrossRefGoogle Scholar
  17. 29.17.
    A. Hermann, R. Goyal, A. Jeltsch: The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites, J. Biol. Chem. 279, 48350–48359 (2004)CrossRefGoogle Scholar
  18. 29.18.
    E. Li, T.H. Bestor, R. Jaenisch: Targeted mutation of the DNA methyltransferase gene results in embryonic lethality, Cell 69(6), 915–926 (1992)CrossRefGoogle Scholar
  19. 29.19.
    M. Okano, D.W. Bell, D.A. Haber, E. Li: DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development, Cell 99(3), 247–257 (1999)CrossRefGoogle Scholar
  20. 29.20.
    J. Turek-Plewa, P.P. Jagodziñski: The role of mammalian DNA methyltransferases in the regulation of gene expression, Cell Mol. Biol. Lett. 10, 631–647 (2005)Google Scholar
  21. 29.21.
    L. Chakalova, E. Debrand, J.A. Mitchell, C.S. Osborne, P. Fraser: Replication and transcription: Shaping the landscape of the genome, Nat. Rev. 6(9), 669–677 (2005)CrossRefGoogle Scholar
  22. 29.22.
    K.L. Arney, A.G. Fisher: Epigenetic aspects of differentiation, J. Cell Sci. 117(19), 4355–4363 (2004)CrossRefGoogle Scholar
  23. 29.23.
    W. Reik: Stability and flexibility of epigenetic gene regulation in mammalian development, Nature 447(7143), 425–432 (2007)CrossRefGoogle Scholar
  24. 29.24.
    J.M. Trasler: Epigenetics in spermatogenesis, Mol. Cell Endocrinol. 306(1–2), 33–36 (2009)CrossRefGoogle Scholar
  25. 29.25.
    M.V. Koerner, D.P. Barlow: Genomic imprinting-an epigenetic gene-regulatory model, Curr. Opin. Genet. Dev. 20(2), 164–170 (2010)CrossRefGoogle Scholar
  26. 29.26.
    S.K. Kota, R. Feil: Epigenetic transitions in germ cell development and meiosis, Dev. Cell 19(5), 675–686 (2010)CrossRefGoogle Scholar
  27. 29.27.
    M. Berdasco, M. Esteller: Aberrant epigenetic landscape in cancer: How cellular identity goes awry, Dev. Cell 19(5), 698–711 (2010)CrossRefGoogle Scholar
  28. 29.28.
    F.P. Fiorentino, M. Macaluso, F. Miranda, M. Montanari, A. Russo, L. Bagella, A. Giordano: CTCF and BORIS regulate Rb2/p130 gene transcription: A novel mechanism and a new paradigm for understanding the biology of lung cancer, Mol. Cancer Res. 9(2), 225–233 (2011)CrossRefGoogle Scholar
  29. 29.29.
    J.G. Herman, S.B. Baylin: Gene silencing in cancer in association with promoter hypermethylation, N. Engl. J. Med. 349(21), 2042–2054 (2003)CrossRefGoogle Scholar
  30. 29.30.
    M.F. Fraga, R. Agrelo, M. Esteller: Cross-talk between aging and cancer: The epigenetic language, Ann. N.Y. Acad. Sci. 1100, 60–74 (2007)CrossRefGoogle Scholar
  31. 29.31.
    F.I. Daniel, K. Cherubini, L.S. Yurgel, M.A. de Figueiredo, F.G. Salum: The role of epigenetic transcription repression and DNA methyltransferases in cancer, Cancer 117(4), 677–687 (2011)CrossRefGoogle Scholar
  32. 29.32.
    F. Chik, M. Szyf: Effects of specific DNMT gene depletion on cancer cell transformation and breast cancer cell invasion; toward selective DNMT inhibitors, Carcinogenesis 32(2), 224–232 (2011)CrossRefGoogle Scholar
  33. 29.33.
    I.P. Pogribny: Epigenetic events in tumorigenesis: Putting pieces together, Exp. Oncol. 32(3), 132–136 (2010)Google Scholar
  34. 29.34.
    N. Sinčć, Z. Herceg: DNA methylation and cancer: Ghosts and angels above the genes, Curr. Opin. Oncol. 23(1), 69–76 (2011)CrossRefGoogle Scholar
  35. 29.35.
    A.P. Feinberg, B. Vogelstein: Hypomethylation of ras oncogenes in primary human cancers, Biochem. Biophys. Res. Commun. 111(1), 47–54 (1983)CrossRefGoogle Scholar
  36. 29.36.
    S.S. Palii, K.D. Robertson: Epigenetic control of tumor suppression, Crit. Rev. Eukaryot. Gene Expr. 17(4), 295–316 (2007)CrossRefGoogle Scholar
  37. 29.37.
    J. Veeck, M. Esteller: Breast cancer epigenetics: From DNA methylation to microRNAs, J. Mammary Gland Biol. Neoplasia 15(1), 5–17 (2010)CrossRefGoogle Scholar
  38. 29.38.
    M. Ehrlich: DNA hypomethylation, cancer, the immunodeficiency, centromeric region instability, facial anomalies syndrome and chromosomal rearrangements, Nutrition 132(8 Suppl), 2424S–2429S (2002)Google Scholar
  39. 29.39.
    M. Ehrlich: DNA methylation and cancer-associated genetic instability, Adv. Exp. Med. Biol. 570, 363–392 (2005)CrossRefGoogle Scholar
  40. 29.40.
    K.R. Ostler, E.M. Davis, S.L. Payne, B.B. Gosalia, J. Expósito-Céspedes, M.M. Le Beau, L.A. Godley: Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins, Oncogene 26(38), 5553–5563 (2007)CrossRefGoogle Scholar
  41. 29.41.
    D.J. Weisenberger, M. Velicescu, J.C. Cheng, F.A. Gonzales, G. Liang, P.A. Jones: Role of the DNA methyltransferase variant DNMT3b3 in DNA methylation, Mol. Cancer Res. 2(1), 62–72 (2004)Google Scholar
  42. 29.42.
    K. Imai, H. Yamamoto: Carcinogenesis and microsatellite instability: The interrelationship between genetics and epigenetics, Carcinogenesis 29(4), 673–680 (2008)CrossRefGoogle Scholar
  43. 29.43.
    P.W. Laird, R. Jaenisch: DNA methylation and cancer, Hum. Mol. Genet. 3, 1487–1495 (1994)Google Scholar
  44. 29.44.
    J. Felsberg, N. Thon, S. Eigenbrod, B. Hentschel, M.C. Sabel, M. Westphal, G. Schackert, F.W. Kreth, T. Pietsch, M. Loeffler, M. Weller, G. Reifenberger, J.C. Tonn: Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6, and PMS2 in paired primary and recurrent glioblastomas, Int. J. Cancer 129(3), 659–670 (2011)CrossRefGoogle Scholar
  45. 29.45.
    K. Ramachandran, H. Miller, E. Gordian, C. Rocha-Lima, R. Singal: Methylation-mediated silencing of TMS1 in pancreatic cancer and its potential contribution to chemosensitivity, Anticancer Res. 30(10), 3919–3925 (2010)Google Scholar
  46. 29.46.
    T.A. Rauch, X. Zhong, X. Wu, M. Wang, K.H. Kernstine, Z. Wang, A.D. Riggs, G.P. Pfeifer: High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer, Proc. Natl. Acad. Sci. USA 105(1), 252–257 (2008)CrossRefGoogle Scholar
  47. 29.47.
    S. Tommasi, D.L. Karm, X. Wu, Y. Yen, G.P. Pfeifer: Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer, Breast Cancer Res. 11(1), R14 (2009)CrossRefGoogle Scholar
  48. 29.48.
    Y. Koga, M. Pelizzola, E. Cheng, M. Krauthammer, M. Sznol, S. Ariyan, D. Narayan, A.M. Molinaro, R. Halaban, S.M. Weissman: Genome-wide screen of promoter methylation identifies novel markers in melanoma, Genome Res. 19(8), 1462–1470 (2009)CrossRefGoogle Scholar
  49. 29.49.
    T. Ushijima: Detection and interpretation of altered methylation patterns in cancer cells, Nat. Rev. Cancer 5, 223–231 (2005)CrossRefGoogle Scholar
  50. 29.50.
    M. Weber, J.J. Davies, D. Wittig, E.J. Oakeley, M. Haase, W.L. Lam, D. Schübeler: Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells, Nat. Genet. 37, 853–862 (2005)CrossRefGoogle Scholar
  51. 29.51.
    T. Nakajima, S. Enomoto, T. Ushijima: DNA methylation: A marker for carcinogen exposure and cancer risk, Environ. Health Prev. Med. 13, 8–15 (2008)CrossRefGoogle Scholar
  52. 29.52.
    M.R. Estécio, J.P. Issa: Dissecting DNA hypermethylation in cancer, FEBS Letters 585(13), 2078–2086 (2011)CrossRefGoogle Scholar
  53. 29.53.
    P.A. Cowin, M. Anglesio, D. Etemadmoghadam, D.L. Bowtell: Profiling the cancer genome, Annu. Rev. Genomics Hum. Genet. 11, 133–159 (2011)CrossRefGoogle Scholar
  54. 29.54.
    R.D. Kornberg, Y. Lorch: Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome, Cell 98(3), 285–294 (1999)CrossRefGoogle Scholar
  55. 29.55.
    T.H. Eickbush, E.N. Moudrianakis: The histone core complex: An octamer assembled by two sets of protein–protein interactions, Biochemistry 17(23), 4955–4964 (1978)CrossRefGoogle Scholar
  56. 29.56.
    A.P. Wolffe: Chromatin structure, Adv. Genome Biol. 5B, 363–414 (1998)CrossRefGoogle Scholar
  57. 29.57.
    P. Cheung, C.D. Allis, P. Sassone-Corsi: Signaling to chromatin through histone modifications, Cell 103, 263–271 (2000)CrossRefGoogle Scholar
  58. 29.58.
    B.D. Strahl, C.D. Allis: The language of covalent histone modifications, Nature 403(6765), 41–45 (2000)CrossRefGoogle Scholar
  59. 29.59.
    T. Kouzarides: Chromatin modifications and their function, Cell 128(4), 693–705 (2007)CrossRefGoogle Scholar
  60. 29.60.
    R. Margueron, D. Reinberg: Chromatin structure and the inheritance of epigenetic information, Nat. Rev. Genet. 11(4), 285–296 (2010)CrossRefGoogle Scholar
  61. 29.61.
    T. Jenuwein, C.D. Allis: Translating the histone code, Science 293(5532), 1074–1080 (2001)CrossRefGoogle Scholar
  62. 29.62.
    B.M. Turner: Histone acetylation and control of gene expression, J. Cell Sci. 99, 13–20 (1991)Google Scholar
  63. 29.63.
    A.P. Wolffe, D. Pruss: Targeting chromatin disruption: Transcription regulators that acetylate histones, Cell 84, 817–819 (1996)CrossRefGoogle Scholar
  64. 29.64.
    P.A. Grant, D. Schieltz, M.G. Pray-Grant, D.J. Steger, J.C. Reese, J.R. Yates, J.L. Workman: A subset of TAFIIs are integral components of the SAGA complex required for nucleosome acetylation and transcriptional stimulation, Cell 94(1), 45–53 (1998)CrossRefGoogle Scholar
  65. 29.65.
    T.M. Fletcher, J.C. Hansen: The nucleosomal array: Structure/function relationships, Crit. Rev. Eukaryot. Gene Expr. 6(2–3), 149–188 (1996)CrossRefGoogle Scholar
  66. 29.66.
    L.C. Lutter, L. Judis, R.F. Paretti: Effects of histone acetylation on chromatin topology in vivo, Mol. Cell Biol. 12(11), 5004–5014 (1992)CrossRefGoogle Scholar
  67. 29.67.
    V.G. Norton, B.S. Imai, P. Yau, E.M. Bradbury: Histone acetylation reduces nucleosome core particle linking number change, Cell 57(3), 449–457 (1998)CrossRefGoogle Scholar
  68. 29.68.
    V.G. Norton, K.W. Marvin, P. Yau, E.M. Bradbury: Nucleosome linking number change controlled by acetylation of histones H3 and H4, J. Biol. Chem. 265(32), 19848–19859 (1990)Google Scholar
  69. 29.69.
    P. Loidl: Histone acetylation: Facts and questions, Chromosoma 103(7), 441–449 (1994)CrossRefGoogle Scholar
  70. 29.70.
    J.E. Brownell, C.D. Allis: An activity gel assay detects a single, catalytically active histone acetyltransferase subunit in Tetrahymena macronuclei, Proc. Natl. Acad. Sci. USA 92(14), 6364–6368 (1995)CrossRefGoogle Scholar
  71. 29.71.
    S.E. Rundlett, A.A. Carmen, R. Kobayashi, S. Bavykin, B.M. Turner, M. Grunstein: HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription, Proc. Natl. Acad. Sci. USA 93(25), 14503–14508 (1996)CrossRefGoogle Scholar
  72. 29.72.
    A.J.M. De Ruijter, A.H. Van Gennip, H.N. Caron, S. Kemp, A.B.P. Van Kuilenburg: Histone deacetylases (HDACs): Characterization of the classical HDAC family, Biochem. J. 370, 737–749 (2003)CrossRefGoogle Scholar
  73. 29.73.
    H. Santos-Rosa, C. Caldas: Chromatin modifier enzymes, the histone code and cancer, Eur. J. Cancer 41, 2381–2402 (2005)CrossRefGoogle Scholar
  74. 29.74.
    M.A. Glozak, E. Seto: Histone deacetylases and cancer, Oncogene 26, 5420–5432 (2007)CrossRefGoogle Scholar
  75. 29.75.
    K.K. Lee, J.L. Workman: Histone acetyltransferase complexes: One size doesnʼt fit all, Mol. Cell Biol. 8, 284–295 (2007)Google Scholar
  76. 29.76.
    M. Dalvai, K. Bystricky: The role of histone modifications and variants in regulating gene expression in breast cancer, J. Mammary Gland Biol. Neoplasia 15, 19–33 (2010)CrossRefGoogle Scholar
  77. 29.77.
    J.C. Black, J.R. Whetstine: Chromatin landscape, Epigenetics 6(1), 9–15 (2011)CrossRefGoogle Scholar
  78. 29.78.
    M. Lachner, R.J. OʼSullivan, T. Jenuwein: An epigenetic road map for histone lysine methylation, J. Cell Sci. 116, 2117–2124 (2003)CrossRefGoogle Scholar
  79. 29.79.
    M. Litt, Y. Qiu, S. Huang: Histone arginine methylations: Their roles in chromatin dynamics and transcriptional regulation, Biosci. Rep. 29(2), 131–141 (2009)CrossRefGoogle Scholar
  80. 29.80.
    K. Agger, J. Christensen, P.A.C. Cloos, K. Helin: The emerging functions of histone demethylases, Curr. Opin. Genet. Dev. 18(2), 159–168 (2008)CrossRefGoogle Scholar
  81. 29.81.
    A.H. Ting, K.M. McGarvey, S.B. Baylin: The cancer epigenome-components and functional correlates, Genes Dev. 20(23), 3215–3231 (2006)CrossRefGoogle Scholar
  82. 29.82.
    C. Sawan, T. Vaissiëre, R. Murr, Z. Herceg: Epigenetic drivers and genetic passengers on the road to cancer, Mutat. Res. 642(1–2), 1–13 (2008)CrossRefGoogle Scholar
  83. 29.83.
    P. Chi, C.D. Allis, G.G. Wang: Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers, Nat. Rev. Cancer 10(7), 457–469 (2010)CrossRefGoogle Scholar
  84. 29.84.
    Y. Kondo: Epigenetic cross-talk between DNA methylation and histone modifications in human cancers, Yonsei Med. J. 50(4), 455–463 (2009)CrossRefGoogle Scholar
  85. 29.85.
    M. Macaluso, C. Cinti, G. Russo, A. Russo, A. Giordano: pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-alpha in breast cancer, Oncogene 22(23), 3511–3517 (2003)CrossRefGoogle Scholar
  86. 29.86.
    M. Macaluso, M. Montanari, P.B. Noto, V. Gregorio, C. Bronner, A. Giordano: Epigenetic modulation of estrogen receptor-alpha by pRb family proteins: A novel mechanism in breast cancer, Cancer Res. 67(16), 7731–7737 (2007)CrossRefGoogle Scholar
  87. 29.87.
    J.M. Wagner, B. Hackanson, M. Lübbert, M. Jung: Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy, Clin. Epigenet. 1(3–4), 117–136 (2010)CrossRefGoogle Scholar
  88. 29.88.
    C. Mund, F. Lyko: Epigenetic cancer therapy: Proof of concept and remaining challenges, BioEssays 32(11), 949–957 (2010)CrossRefGoogle Scholar
  89. 29.89.
    T.K. Kelly, D.D. De Carvalho, P.A. Jones: Epigenetic modifications as therapeutic targets, Nat. Biotechnol. 28, 1069–1078 (2010)CrossRefGoogle Scholar
  90. 29.90.
    J. Peedicayil: Epigenetic therapy – a new development in pharmacology, Indian J. Med. Res. 123, 17–24 (2006)Google Scholar
  91. 29.91.
    A.J. Davis, K.A. Gelmon, L.L. Siu, M.J. Moore, C.D. Britten, N. Mistry: Phase I and pharmacologic study of the human DNA methyltransferase antisense oligodeoxynucleotide MG98 given as 21-day continuous infusion every 4 weeks, Investig. New Drugs 21, 85–97 (2003)CrossRefGoogle Scholar
  92. 29.92.
    D.J. Stewart, R.C. Donehowe, E.A. Eisenhaue, N. Wainman, A.K. Shah, C. Bonfils: A phase I pharmacokinetic and pharmacodynamic study of the DNA methyltransferase 1 inhibitor MG98 administered twice weekly, Ann. Oncol. 14, 766–774 (2003)CrossRefGoogle Scholar
  93. 29.93.
    R.B. Klisovic, W. Stock, S. Cataland, M.I. Klisovic, S. Liu, W. Blum: A phase I biological study of MG98, an oligodeoxynucleotide antisense to DNA methyltransferase 1, in patients with high-risk myelodysplasia and acute myeloid leukemia, Clin. Cancer Res. 12, 2444–2449 (2008)CrossRefGoogle Scholar
  94. 29.94.
    J.E. Bolden, M.J. Pearl, R.W. Johnstone: Anticancer activities of histone deacetylase inhibitors, Nat. Rev. Drug Discov. 5(9), 769–784 (2006)CrossRefGoogle Scholar
  95. 29.95.
    A. Mai, S. Massa, D. Rotili, I. Cerbara, S. Valente, R. Pezzi, S. Simeoni, R. Ragno: Histone deacetylation in epigenetics: An attractive target for anticancer therapy, Med. Res. Rev. 25(3), 261–309 (2005)CrossRefGoogle Scholar
  96. 29.96.
    L.S. Kristensen, H.M. Nielsen, L.L. Hansen: Epigenetics and cancer treatment, Eur. J. Pharmacol. 625(1–3), 131–142 (2009)CrossRefGoogle Scholar
  97. 29.97.
    F. Thaler, S. Minucci: Next generation histone deacetylase inhibitors: The answer to the search for optimized epigenetic therapies?, Exp. Opin. Drug Discov. 6(4), 393–404 (2011)CrossRefGoogle Scholar
  98. 29.98.
    S. Shankar, R.K. Srivastava: Histone deacetylase inhibitors: Mechanisms and clinical significance in cancer: HDAC inhibitor-induced apoptosis, Adv. Exp. Med. Biol. 615, 261–298 (2008)CrossRefGoogle Scholar
  99. 29.99.
    P.A. Marks: Discovery and development of SAHA as an anticancer agent, Oncogene 26, 1351–1356 (2007)CrossRefGoogle Scholar
  100. 29.100.
    V.M. Richon: Cancer biology: Mechanism of antitumour action of vorinostat (suberoylanilide hydroxamic acid), a novel histone deacetylase inhibitor, Br. J. Cancer 95(S1), S2–S6 (2006)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2014

Authors and Affiliations

  1. 1.Biology-Center for BiotechnologyTemple UniversityPhiladelphiaUSA
  2. 2.Biology – Center for BiotechnologyTemple UniversityPhiladelphiaUSA
  3. 3.Biology – Center for BiotechnologyTemple UniversityPhiladelphiaUSA

Personalised recommendations