• Mehmet Gunduz
  • Muradiye Acar
  • Kubra Erdogan
  • Elif Nihat Cetin
  • Esra Gunduz


Epigenetic modifications are defined as the study of heritable changes in phenotype that do not involve alterations in the DNA sequence. DNA methylation, posttranslational modifications of the histone proteins, and miRNAs are regulating the expression of genes as well as drug-metabolizing genes. Epigenetic regulation is essential for normal developmental and cellular processes. Conversely, abnormal epigenetic regulation is a character of complex diseases, including cancer, hematological malignancies, psychiatric disorders, and other diseases. Pharmaco-epigenomics is a novel discipline and involves the study of epigenetic factors in the interpersonal variation to drugs. Epigenetic biomarkers can be used to diagnose disease, estimate disease progression, or predict interpersonal variations in response to therapy. Unlike genetic alterations, changes in epigenetic machinery are reversible, and this reversible characteristic makes them an attractive therapeutic targets.


HDAC Inhibitor Acute Myelogenous Leukemia Rett Syndrome DNMT Inhibitor Epigenetic Therapy 


  1. Abel T, Zukin RS (2008) Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol 8(1):57–64PubMedCentralPubMedCrossRefGoogle Scholar
  2. Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355PubMedCrossRefGoogle Scholar
  3. Aparicio A, Weber JS (2002) Review of the clinical experience with 5-azacytidine and 5-aza-2′-deoxycytidine in solid tumors. Curr Opin Investig Drugs 3(4):627–633PubMedGoogle Scholar
  4. Baer-Dubowska W, Majchrzak-Celinska A, Cichocki M (2011) Pharmocoepigenetics: a new approach to predicting individual drug responses and targeting new drugs. Pharmacol Rep 63(2):293–304PubMedGoogle Scholar
  5. Baker EK, Johnstone RW, Zalcberg JR et al (2005) Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs. Oncogene 24(54):8061–8075PubMedCrossRefGoogle Scholar
  6. Ballestar E, Paz MF, Valle L et al (2003) Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer. EMBO J 22(23):6335–6345PubMedCentralPubMedCrossRefGoogle Scholar
  7. Bates GP (2001) Huntington’s disease. Exploiting expression. Nature 413(6857):691, 693–694PubMedCrossRefGoogle Scholar
  8. Belinsky SA, Nikula KJ, Palmisano WA et al (1998) Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA 95(20):11891–11896PubMedCentralPubMedCrossRefGoogle Scholar
  9. Bender CM, Zingg JM, Jones PA (1998) DNA methylation as a target for drug design. Pharm Res 15(2):175–187PubMedCrossRefGoogle Scholar
  10. Billam M, Sobolewski MD, Davidson NE (2010) Effects of a novel DNA methyltransferase inhibitor zebularine on human breast cancer cells. Breast Cancer Res Treat 120(3):581–592PubMedCrossRefGoogle Scholar
  11. Bjornsson HT, Sigurdsson MI, Fallin MD et al (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299(24):2877–2883PubMedCentralPubMedCrossRefGoogle Scholar
  12. Brueckner B, Garcia Boy R, Siedlecki P et al (2005) Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res 65(14):6305–6311PubMedCrossRefGoogle Scholar
  13. Candelaria M, de la Cruz-Hernandez E, Perez-Cardenas E et al (2010) Pharmacogenetics and pharmacoepigenetics of gemcitabine. Med Oncol 27(4):1133–1143PubMedCrossRefGoogle Scholar
  14. Carey N, La Thangue NB (2006) Histone deacetylase inhibitors: gathering pace. Curr Opin Pharmacol 6(4):369–375PubMedCrossRefGoogle Scholar
  15. Chim CS, Wong AS, Kwong YL (2004) Epigenetic dysregulation of the Jak/STAT pathway by frequent aberrant methylation of SHP1 but not SOCS1 in acute leukaemias. Ann Hematol 83(8):527–532PubMedGoogle Scholar
  16. Cimino G, Moir DT, Canaani O et al (1991) Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations. Cancer Res 51(24):6712–6714PubMedGoogle Scholar
  17. Claes B, Buysschaert I, Lambrechts D (2010) Pharmaco-epigenomics: discovering therapeutic approaches and biomarkers for cancer therapy. Heredity 105(1):152–160PubMedCrossRefGoogle Scholar
  18. Costa FF (2008) Non-coding RNAs, epigenetics and complexity. Gene 410(1):9–17PubMedCrossRefGoogle Scholar
  19. Csoka AB, Szyf M (2009) Epigenetic side-effects of common pharmaceuticals: a potential new field in medicine and pharmacology. Med Hypotheses 73(5):770–780PubMedCrossRefGoogle Scholar
  20. Dennis C (2003) Epigenetics and disease: altered states. Nature 421(6924):686–688PubMedCrossRefGoogle Scholar
  21. Donkena KV, Young CY, Tindall DJ (2010) Oxidative stress and DNA methylation in prostate cancer. Obstet Gynecol Int 2010, Article ID 302051, doi: 10.1155/2010/302051
  22. Durst KL, Hiebert SW (2004) Role of RUNX family members in transcriptional repression and gene silencing. Oncogene 23(24):4220–4224PubMedCrossRefGoogle Scholar
  23. Eden A, Gaudet F, Waghmare A et al (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300(5618):455PubMedCrossRefGoogle Scholar
  24. Ernst P, Wang J, Huang M et al (2001) MLL and CREB bind cooperatively to the nuclear coactivator CREB-binding protein. Mol Cell Biol 21(7):2249–2258PubMedCentralPubMedCrossRefGoogle Scholar
  25. Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8(4):286–298PubMedCrossRefGoogle Scholar
  26. Esteller M, Corn PG, Urena JM et al (1998) Inactivation of glutathione S-transferase P1 gene by promoter hypermethylation in human neoplasia. Cancer Res 58(20):4515–4518PubMedGoogle Scholar
  27. Fabbri M, Calin GA (2010) Epigenetics and miRNAs in human cancer. Adv Genet 70:87–99PubMedCrossRefGoogle Scholar
  28. Fang MZ, Wang Y, Ai N et al (2003) Tea polyphenol (−)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63(22):7563–7570PubMedGoogle Scholar
  29. Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447(7143):433–440PubMedCrossRefGoogle Scholar
  30. Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301(5895):89–92PubMedCrossRefGoogle Scholar
  31. Fog CK, Jensen KT, Lund AH (2007) Chromatin-modifying proteins in cancer. APMIS 115(10):1060–1089PubMedCrossRefGoogle Scholar
  32. Freeman DJ, Juan T, Reiner M et al (2008) Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone. Clin Colorectal Cancer 7(3):184–190PubMedCrossRefGoogle Scholar
  33. Gaudet F, Hodgson JG, Eden A et al (2003) Induction of tumors in mice by genomic hypomethylation. Science 300(5618):489–492PubMedCrossRefGoogle Scholar
  34. Giacomini KM, Huang SM, Tweedie DJ et al (2010) Membrane transporters in drug development. Nat Rev Drug Discov 9(3):215–236PubMedCrossRefGoogle Scholar
  35. Glover AB, Leyland-Jones BR, Chun HG et al (1987) Azacitidine: 10 years later. Cancer Treat Rep 71(7–8):737–746PubMedGoogle Scholar
  36. Gomez A, Ingelman-Sundberg M (2009) Pharmacoepigenetics: its role in interindividual differences in drug response. Clin Pharmacol Ther 85(4):426–430PubMedCrossRefGoogle Scholar
  37. Gowher H, Jeltsch A (2004) Mechanism of inhibition of DNA methyltransferases by cytidine analogs in cancer therapy. Cancer Biol Ther 3(11):1062–1068PubMedCrossRefGoogle Scholar
  38. Guengerich FP (2006) Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J 8(1):E101–E111PubMedCentralPubMedCrossRefGoogle Scholar
  39. Hackanson B, Robbel C, Wijermans P et al (2005) In vivo effects of decitabine in myelodysplasia and acute myeloid leukemia: review of cytogenetic and molecular studies. Ann Hematol 84(Suppl 1):32–38PubMedCrossRefGoogle Scholar
  40. Hamm CA, Costa FF (2011) The impact of epigenomics on future drug design and new therapies. Drug Discov Today 16(13–14):626–635PubMedCrossRefGoogle Scholar
  41. Hamm CA, Xie H, Costa FF et al (2009) Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2′-deoxycytidine results in increased tumorigenicity. PLoS One 4(12):e8340PubMedCentralPubMedCrossRefGoogle Scholar
  42. Hammons GJ, Yan-Sanders Y, Jin B et al (2001) Specific site methylation in the 5′-flanking region of CYP1A2 interindividual differences in human livers. Life Sci 69(7):839–845PubMedCrossRefGoogle Scholar
  43. Hauser AT, Jung M (2008) Targeting epigenetic mechanisms: potential of natural products in cancer chemoprevention. Planta Med 74(13):1593–1601PubMedCrossRefGoogle Scholar
  44. Hellebrekers DM, Jair KW, Vire E et al (2006) Angiostatic activity of DNA methyltransferase inhibitors. Mol Cancer Ther 5(2):467–475PubMedCrossRefGoogle Scholar
  45. Herman JG, Latif F, Weng Y et al (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 91(21):9700–9704PubMedCentralPubMedCrossRefGoogle Scholar
  46. Hermann A, Gowher H, Jeltsch A (2004) Biochemistry and biology of mammalian DNA methyltransferases. Cell Mol Life Sci 61(19–20):2571–2587PubMedCrossRefGoogle Scholar
  47. Hobert O (2008) Gene regulation by transcription factors and microRNAs. Science 319(5871):1785–1786PubMedCrossRefGoogle Scholar
  48. Ibanez de Caceres I, Cortes-Sempere M, Moratilla C et al (2010) IGFBP-3 hypermethylation-derived deficiency mediates cisplatin resistance in non-small-cell lung cancer. Oncogene 29(11):1681–1690PubMedCrossRefGoogle Scholar
  49. Ingelman-Sundberg M, Gomez A (2010) The past, present and future of pharmacoepigenomics. Pharmacogenomics 11(5):625–627PubMedCrossRefGoogle Scholar
  50. Issa JP (1999) Aging, DNA methylation and cancer. Crit Rev Oncol Hematol 32(1):31–43PubMedCrossRefGoogle Scholar
  51. Issa JP (2004) CpG island methylator phenotype in cancer. Nat Rev Cancer 4(12):988–993PubMedCrossRefGoogle Scholar
  52. Jarmalaite S, Andrekute R, Scesnaite A et al (2010) Promoter hypermethylation in tumour suppressor genes and response to interleukin-2 treatment in bladder cancer: a pilot study. J Cancer Res Clin Clin Oncol 136(6):847–854CrossRefGoogle Scholar
  53. Jeronimo C, Usadel H, Henrique R et al (2001) Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ-confined prostate adenocarcinoma. J Natl Cancer Inst 93(22):1747–1752PubMedCrossRefGoogle Scholar
  54. Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3(6):415–428PubMedGoogle Scholar
  55. Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128(4):683–692PubMedCrossRefGoogle Scholar
  56. Jones PA, Taylor SM (1980) Cellular differentiation, cytidine analogs and DNA methylation. Cell 20(1):85–93PubMedCrossRefGoogle Scholar
  57. Juttermann R, Li E, Jaenisch R (1994) Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci USA 91(25):11797–11801PubMedCentralPubMedCrossRefGoogle Scholar
  58. Kastrup IB, Worm J, Ralfkiaer E et al (2008) Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma. Eur J Haematol 80(1):61–66PubMedGoogle Scholar
  59. Kelly TK, De Carvalho DD, Jones PA (2010) Epigenetic modifications as therapeutic targets. Nat Biotechnol 28(10):1069–1078PubMedCrossRefGoogle Scholar
  60. Khambata-Ford S, Garrett CR, Meropol NJ et al (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25(22):3230–3237PubMedCrossRefGoogle Scholar
  61. Khan O, La Thangue NB (2008) Drug Insight: histone deacetylase inhibitor-based therapies for cutaneous T-cell lymphomas. Nat Clin Pract Oncol 5(12):714–726PubMedCrossRefGoogle Scholar
  62. Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705PubMedCrossRefGoogle Scholar
  63. Levenson JM, Sweatt JD (2005) Epigenetic mechanisms in memory formation. Nat Rev Neurosci 6(2):108–118PubMedCrossRefGoogle Scholar
  64. Li Q, Ahuja N, Burger PC et al (1999) Methylation and silencing of the Thrombospondin-1 promoter in human cancer. Oncogene 18(21):3284–3289PubMedCrossRefGoogle Scholar
  65. Ling G, Wei Y, Ding X (2007) Transcriptional regulation of human CYP2A13 expression in the respiratory tract by CCAAT/enhancer binding protein and epigenetic modulation. Mol Pharmacol 71(3):807–816PubMedCrossRefGoogle Scholar
  66. Mack GS (2006) Epigenetic cancer therapy makes headway. J Natl Cancer Inst 98(20):1443–1444PubMedCrossRefGoogle Scholar
  67. Mano H (2008) Epigenetic abnormalities in cardiac hypertrophy and heart failure. Environ Health Prev Med 13(1):25–29PubMedCentralPubMedCrossRefGoogle Scholar
  68. Marks P, Rifkind RA, Richon VM et al (2001) Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 1(3):194–202PubMedCrossRefGoogle Scholar
  69. Martens JW, Margossian AL, Schmitt M et al (2009) DNA methylation as a biomarker in breast cancer. Future Oncol 5(8):1245–1256PubMedCrossRefGoogle Scholar
  70. Mateo Leach I, van der Harst P, de Boer RA (2010) Pharmacoepigenetics in heart failure. Curr Heart Fail Rep 7(2):83–90PubMedCentralPubMedCrossRefGoogle Scholar
  71. Mattick JS (2004) RNA regulation: a new genetics? Nat Rev Genet 5(4):316–323PubMedCrossRefGoogle Scholar
  72. Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430(7000):631–639PubMedCentralPubMedCrossRefGoogle Scholar
  73. Melki JR, Vincent PC, Clark SJ (1999) Cancer-specific region of hypermethylation identified within the HIC1 putative tumour suppressor gene in acute myeloid leukaemia. Leukemia 13(6):877–883PubMedCrossRefGoogle Scholar
  74. Milne TA, Briggs SD, Brock HW et al (2002) MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol Cell 10(5):1107–1117PubMedCrossRefGoogle Scholar
  75. Minucci S, Pelicci PG (2006) Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 6(1):38–51PubMedCrossRefGoogle Scholar
  76. Mund C, Brueckner B, Lyko F (2006) Reactivation of epigenetically silenced genes by DNA methyltransferase inhibitors: basic concepts and clinical applications. Epigenetics 1(1):7–13PubMedCrossRefGoogle Scholar
  77. Nakajima M, Yokoi T (2011) MicroRNAs from biology to future pharmacotherapy: regulation of cytochrome P450s and nuclear receptors. Pharmacol Ther 131(3):330–337PubMedCrossRefGoogle Scholar
  78. Nakamura T, Mori T, Tada S et al (2002) ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell 10(5):1119–1128PubMedCrossRefGoogle Scholar
  79. Oki Y, Issa JP (2010) Epigenetic mechanisms in AML – a target for therapy. Cancer Treat Res 145:19–40PubMedCrossRefGoogle Scholar
  80. Okino ST, Pookot D, Li LC et al (2006) Epigenetic inactivation of the dioxin-responsive cytochrome P4501A1 gene in human prostate cancer. Cancer Res 66(15):7420–7428PubMedCrossRefGoogle Scholar
  81. Pandey DP, Picard D (2009) miR-22 inhibits estrogen signaling by directly targeting the estrogen receptor alpha mRNA. Mol Cell Biol 29(13):3783–3790PubMedCentralPubMedCrossRefGoogle Scholar
  82. Peaston AE, Whitelaw E (2006) Epigenetics and phenotypic variation in mammals. Mamm Genome 17(5):365–374PubMedCrossRefGoogle Scholar
  83. Peedicayil J (2006) Epigenetic therapy – a new development in pharmacology. Indian J Med Res 123(1):17–24PubMedGoogle Scholar
  84. Peedicayil J (2008) Pharmacoepigenetics and pharmacoepigenomics. Pharmacogenomics 9(12):1785–1786PubMedCrossRefGoogle Scholar
  85. Pogribny IP, Beland FA (2009) DNA hypomethylation in the origin and pathogenesis of human diseases. Cell Mol Life Sci 66(14):2249–2261PubMedCrossRefGoogle Scholar
  86. Poulter MO, Du L, Weaver IC et al (2008) GABAA receptor promoter hypermethylation in suicide brain: implications for the involvent of epigenetic processes. Biol Psychiatry 64(8):645–652PubMedCrossRefGoogle Scholar
  87. Ray-Gallet D, Almouzni G (2010) Nucleosome dynamics and histone variants. Essays Biochem 48(1):75–87PubMedCrossRefGoogle Scholar
  88. Richards EJ, Elgin SC (2002) Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects. Cell 108(4):489–500PubMedCrossRefGoogle Scholar
  89. Rodriguez-Antona C, Gomez A, Karlgren M et al (2010) Molecular genetics and epigenetics of the cytochrome P450 gene family and its relevance for cancer risk and treatment. Hum Genet 127(1):1–17PubMedCrossRefGoogle Scholar
  90. Santi DV, Norment A, Garrett CE (1984) Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-azacytosine. Proc Natl Acad Sci USA 81(22):6993–6997PubMedCentralPubMedCrossRefGoogle Scholar
  91. Sasaki H, Matsui Y (2008) Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet 9(2):129–140PubMedCrossRefGoogle Scholar
  92. Scandura JM, Boccuni P, Cammenga J et al (2002) Transcription factor fusions in acute leukemia: variations on a theme. Oncogene 21(21):3422–3444PubMedCrossRefGoogle Scholar
  93. Schroen B, Heymans S (2009) MicroRNAs and beyond: the heart reveals its treasures. Hypertension 54(6):1189–1194PubMedCrossRefGoogle Scholar
  94. Sebova K, Fridrichova I (2010) Epigenetic tools in potential anticancer therapy. Anticancer Drugs 21(6):565–577PubMedCrossRefGoogle Scholar
  95. Shi Y (2007) Histone lysine demethylases: emerging roles in development, physiology and disease. Nat Rev Genet 8(11):829–833PubMedCrossRefGoogle Scholar
  96. Silverman LR, Mufti GJ (2005) Methylation inhibitor therapy in the treatment of myelodysplastic syndrome. Nat Clin Pract Oncol 2(Suppl 1):S12–S23PubMedCrossRefGoogle Scholar
  97. Stamatoyannopoulos JA, Dunham I (2008) Epigenomics at the tipping point. Foreword. Pharmacogenomics 9(12):1781–1783PubMedCrossRefGoogle Scholar
  98. Sugars KL, Rubinsztein DC (2003) Transcriptional abnormalities in Huntington disease. Trends Genet 19(5):233–238PubMedCrossRefGoogle Scholar
  99. Toyota M, Issa JP (1999) CpG island methylator phenotypes in aging and cancer. Semin Cancer Biol 9(5):349–357PubMedCrossRefGoogle Scholar
  100. Toyota M, Ohe-Toyota M, Ahuja N et al (2000) Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proc Natl Acad Sci USA 97(2):710–715PubMedCentralPubMedCrossRefGoogle Scholar
  101. Toyota M, Kopecky KJ, Toyota MO et al (2001) Methylation profiling in acute myeloid leukemia. Blood 97(9):2823–2829PubMedCrossRefGoogle Scholar
  102. Toyota M, Suzuki H, Yamashita T et al (2009) Cancer epigenomics: implications of DNA methylation in personalized cancer therapy. Cancer Sci 100(5):787–791PubMedCrossRefGoogle Scholar
  103. Tsankova NM, Berton O, Renthal W et al (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9(4):519–525PubMedCrossRefGoogle Scholar
  104. Uchida T, Kinoshita T, Nagai H et al (1997) Hypermethylation of the p15INK4B gene in myelodysplastic syndromes. Blood 90(4):1403–1409PubMedGoogle Scholar
  105. Urdinguio RG, Sanchez-Mut JV, Esteller M (2009) Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol 8(11):1056–1072PubMedCrossRefGoogle Scholar
  106. Wood MA, Hawk JD, Abel T (2006) Combinatorial chromatin modifications and memory storage: a code for memory? Learn Mem 13(3):241–244PubMedCentralPubMedCrossRefGoogle Scholar
  107. Worm J, Kirkin AF, Dzhandzhugazyan KN et al (2001) Methylation-dependent silencing of the reduced folate carrier gene in inherently methotrexate-resistant human breast cancer cells. J Biol Chem 276(43):39990–40000PubMedCrossRefGoogle Scholar
  108. Xia ZB, Anderson M, Diaz MO et al (2003) MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. Proc Natl Acad Sci USA 100(14):8342–8347PubMedCentralPubMedCrossRefGoogle Scholar
  109. Youssef EM, Lotan D, Issa JP et al (2004) Hypermethylation of the retinoic acid receptor-beta (2) gene in head and neck carcinogenesis. Clin Cancer Res 10(5):1733–1742PubMedCrossRefGoogle Scholar
  110. Yu AM (2009) Role of microRNAs in the regulation of drug metabolism and disposition. Expert Opin Drug Metab Toxicol 5(12):1513–1528PubMedCrossRefGoogle Scholar
  111. Yu A-M, Pan Y-Z (2012) Noncoding microRNAs: small RNAs play a big role in regulation of ADME? Acta Pharm Sin B 2(2):93–101Google Scholar
  112. Yu L, Liu C, Vandeusen J et al (2005) Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nat Genet 37(3):265–274PubMedCrossRefGoogle Scholar
  113. Zeleznik-Le NJ, Harden AM, Rowley JD (1994) 11q23 translocations split the “AT-hook” cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc Natl Acad Sci USA 91(22):10610–10614PubMedCentralPubMedCrossRefGoogle Scholar
  114. Zhang B, Farwell MA (2008) microRNAs: a new emerging class of players for disease diagnostics and gene therapy. J Cell Mol Med 12(1):3–21PubMedCrossRefGoogle Scholar

Copyright information

© Springer India 2013

Authors and Affiliations

  • Mehmet Gunduz
    • 1
  • Muradiye Acar
    • 1
  • Kubra Erdogan
    • 1
  • Elif Nihat Cetin
    • 1
  • Esra Gunduz
    • 1
  1. 1.Department of Medical Genetics, Faculty of MedicineTurgut Ozal UniversityAnkaraTurkey

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