Epigenetics and Human Disease

  • Angeliki Magklara
  • Stavros LomvardasEmail author


The completion of the Human Genome Project has advanced our understanding of the biological processes involved in health and disease. The increasing amount of whole-genome sequencing data becoming available from healthy and affected individuals has pinpointed variations in the DNA sequence, like single-nucleotide polymorphisms (SNPs), that may help to explain differences in phenotype, as well as in disease susceptibility and resistance. On the other hand, it is becoming increasingly apparent that the DNA-stored information alone cannot be the sole determinant of human variation and disease. The extreme phenotypic variability that characterizes the >250 different cell types in the human body, where all cells carry the same genetic information, as well as the high monozygotic discordance rates for human diseases clearly indicate so. Nowadays, it is well established that the epigenome exerts an additional layer of regulation on gene expression and can “manipulate” the same genetic code into producing distinct phenotypes. The epigenome shows far greater plasticity than the genome and contributes significantly to development and differentiation by responding to environmental stimuli. Errors in epigenetic programming caused by genetic defects and/or environmental factors have been directly implicated with human disease. In this chapter, we describe known epigenetic mechanisms and discuss the aberrant epigenetic patterns that characterize several human diseases.


Epigenetics Chromatin DNA methylation HAT HDAC HDM HMT miRNAs DNA hypermethylation Autoimmune diseases Systemic lupus erythematosus Rett syndrome MeCP2 Acute lymphoblastic leukemia Acute myeloid leukemia 



Autoimmune diseases


Acute lymphoblastic leukemia


Acute myeloid leukemia


Brain-derived neurotrophic factor


Cluster of differentiation


Cadherin 3 type 1, P-cadherin


Cyclin-dependent kinase inhibitor 2A


Chromatin immunoprecipitation


Distal-less homeobox 5


Distal-less homeobox 6


DNA methyltransferases


DOT1-like histone H3 methyltransferase


Growth arrest and DNA-damage-inducible protein alpha


Glutathione S-transferase-π1


Histone acetyltransferases


Histone deacetylases


Histone demethylases


Histone methyltransferases


Homeobox A9


Insulin-like growth factor 2


Integrin alpha L


Long interspersed nuclear elements


Loss of imprinting


Methyl-binding domain


Mdm2 p53 binding protein homolog


Methyl-CpG binding protein 2


O-6-methylguanine-DNA methyltransferase


Major histocompatibility complex




Mixed-lineage leukemia 1 gene



Nuclear localization signal




Tumor protein p53


Programmed cell death 1

Pol II

RNA polymerase II


Perforin 1


RNA-induced silencing complex


Rett syndrome


Systemic lupus erythematosus


Single-nucleotide polymorphisms


SRY (sex-determining region Y)-box 4


T cell antigen receptor


Transcriptional repression domain


Trichostatin A


Ubiquitin protein ligase E3A


X chromosome inactivation


X inactivation


  1. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23:185–188PubMedCrossRefGoogle Scholar
  2. Balada E, Ordi-Ros J, Serrano-Acedo S, Martinez-Lostao L, Rosa-Leyva M, Vilardell-Tarres M (2008) Transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus. Immunology 124:339–347PubMedCrossRefGoogle Scholar
  3. Ballestar E, Esteller M, Richardson BC (2006) The epigenetic face of systemic lupus erythematosus. J Immunol 176:7143–7147PubMedGoogle Scholar
  4. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381–395PubMedCrossRefGoogle Scholar
  5. Barreto G, Schafer A, Marhold J, Stach D, Swaminathan SK, Handa V, Doderlein G, Maltry N, Wu W, Lyko F, Niehrs C (2007) Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature 445:671–675PubMedCrossRefGoogle Scholar
  6. 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 129:823–837PubMedCrossRefGoogle Scholar
  7. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297PubMedCrossRefGoogle Scholar
  8. Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6:107–116PubMedCrossRefGoogle Scholar
  9. Berdasco M, Esteller M (2010) Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev Cell 19:698–711PubMedCrossRefGoogle Scholar
  10. Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412PubMedCrossRefGoogle Scholar
  11. Bettstetter M, Woenckhaus M, Wild PJ, Rummele P, Blaszyk H, Hartmann A, Hofstadter F, Dietmaier W (2005) Elevated nuclear maspin expression is associated with microsatellite instability and high tumour grade in colorectal cancer. J Pathol 205:606–614PubMedCrossRefGoogle Scholar
  12. Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH (2001) Dnmt3L and the establishment of maternal genomic imprints. Science 294:2536–2539PubMedCrossRefGoogle Scholar
  13. Brooks WH, Le Dantec C, Pers JO, Youinou P, Renaudineau Y (2010) Epigenetics and autoimmunity. J Autoimmun 34:J207–J219PubMedCrossRefGoogle Scholar
  14. Calvanese V, Lara E, Kahn A, Fraga MF (2009) The role of epigenetics in aging and age-related diseases. Ageing Res Rev 8:268–276PubMedCrossRefGoogle Scholar
  15. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY (2008) MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320:1224–1229PubMedCrossRefGoogle Scholar
  16. Chahrour M, Zoghbi HY (2007) The story of Rett syndrome: from clinic to neurobiology. Neuron 56:422–437PubMedCrossRefGoogle Scholar
  17. Chen ZX, Mann JR, Hsieh CL, Riggs AD, Chedin F (2005) Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family. J Cell Biochem 95:902–917PubMedCrossRefGoogle Scholar
  18. Cheng MF, Lee CH, Hsia KT, Huang GS, Lee HS (2009) Methylation of histone H3 lysine 27 associated with apoptosis in osteosarcoma cells induced by staurosporine. Histol Histopathol 24:1105–1111PubMedGoogle Scholar
  19. Cheung WL, Ajiro K, Samejima K, Kloc M, Cheung P, Mizzen CA, Beeser A, Etkin LD, Chernoff J, Earnshaw WC, Allis CD (2003) Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. Cell 113:507–517PubMedCrossRefGoogle Scholar
  20. Chi P, Allis CD, Wang GG (2010) Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer 10:457–469PubMedCrossRefGoogle Scholar
  21. Christodoulou J, Weaving LS (2003) MECP2 and beyond: phenotype-genotype correlations in Rett syndrome. J Child Neurol 18:669–674PubMedCrossRefGoogle Scholar
  22. Clayton-Smith J, Watson P, Ramsden S, Black GC (2000) Somatic mutation in MECP2 as a non-fatal neurodevelopmental disorder in males. Lancet 356:830–832PubMedCrossRefGoogle Scholar
  23. D’Cruz DP, Khamashta MA, Hughes GR (2007) Systemic lupus erythematosus. Lancet 369:587–596PubMedCrossRefGoogle Scholar
  24. Daser A, Rabbitts TH (2005) The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis. Semin Cancer Biol 15:175–188PubMedCrossRefGoogle Scholar
  25. Davalos V, Esteller M (2010) MicroRNAs and cancer epigenetics: a macrorevolution. Curr Opin Oncol 22:35–45PubMedCrossRefGoogle Scholar
  26. De Smet C, Lurquin C, Lethe B, Martelange V, Boon T (1999) DNA methylation is the primary silencing mechanism for a set of germ line- and tumor-specific genes with a CpG-rich promoter. Mol Cell Biol 19:7327–7335PubMedGoogle Scholar
  27. Deng C, Lu Q, Zhang Z, Rao T, Attwood J, Yung R, Richardson B (2003) Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling. Arthritis Rheum 48:746–756PubMedCrossRefGoogle Scholar
  28. Dieker JW, Fransen JH, van Bavel CC, Briand JP, Jacobs CW, Muller S, Berden JH, van der Vlag J (2007) Apoptosis-induced acetylation of histones is pathogenic in systemic lupus erythematosus. Arthritis Rheum 56:1921–1933PubMedCrossRefGoogle Scholar
  29. Eapen V (2011) Genetic basis of autism: is there a way forward? Curr Opin Psychiatry 24:226–236PubMedCrossRefGoogle Scholar
  30. Eden A, Gaudet F, Waghmare A, Jaenisch R (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300:455PubMedCrossRefGoogle Scholar
  31. Esteller M (2005) Aberrant DNA methylation as a cancer-inducing mechanism. Annu Rev Pharmacol Toxicol 45:629–656PubMedCrossRefGoogle Scholar
  32. Esteller M (2008) Epigenetics in cancer. N Engl J Med 358:1148–1159PubMedCrossRefGoogle Scholar
  33. Farazi TA, Spitzer JI, Morozov P, Tuschl T (2011) miRNAs in human cancer. J Pathol 223:102–115PubMedCrossRefGoogle Scholar
  34. Feinberg AP (2004) The epigenetics of cancer etiology. Semin Cancer Biol 14:427–432PubMedCrossRefGoogle Scholar
  35. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7:21–33PubMedCrossRefGoogle Scholar
  36. Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92PubMedCrossRefGoogle Scholar
  37. Fernandez-Morera JL, Calvanese V, Rodriguez-Rodero S, Menendez-Torre E, Fraga MF (2010) Epigenetic regulation of the immune system in health and disease. Tissue Antigens 76:431–439PubMedCrossRefGoogle Scholar
  38. Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K et al (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37:391–400PubMedCrossRefGoogle Scholar
  39. Fraga MF, Herranz M, Espada J, Ballestar E, Paz MF, Ropero S, Erkek E, Bozdogan O, Peinado H, Niveleau A et al (2004) A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors. Cancer Res 64:5527–5534PubMedCrossRefGoogle Scholar
  40. Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, Bestor TH (2006) Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311:395–398PubMedCrossRefGoogle Scholar
  41. Gorelik G, Fang JY, Wu A, Sawalha AH, Richardson B (2007) Impaired T cell protein kinase C delta activation decreases ERK pathway signaling in idiopathic and hydralazine-induced lupus. J Immunol 179:5553–5563PubMedGoogle Scholar
  42. Grafodatskaya D, Chung B, Szatmari P, Weksberg R (2010) Autism spectrum disorders and epigenetics. J Am Acad Child Adolesc Psychiatry 49:794–809PubMedCrossRefGoogle Scholar
  43. Grewal SI, Jia S (2007) Heterochromatin revisited. Nat Rev Genet 8:35–46PubMedCrossRefGoogle Scholar
  44. Guy J, Cheval H, Selfridge J, Bird A (2011) The role of MeCP2 in the brain. Annu Rev Cell Dev Biol 27:631–652PubMedCrossRefGoogle Scholar
  45. Guy J, Gan J, Selfridge J, Cobb S, Bird A (2007) Reversal of neurological defects in a mouse model of Rett syndrome. Science 315:1143–1147PubMedCrossRefGoogle Scholar
  46. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70PubMedCrossRefGoogle Scholar
  47. Hang CT, Yang J, Han P, Cheng HL, Shang C, Ashley E, Zhou B, Chang CP (2010) Chromatin regulation by Brg1 underlies heart muscle development and disease. Nature 466:62–67PubMedCrossRefGoogle Scholar
  48. Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW et al (2009) Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459:108–112PubMedCrossRefGoogle Scholar
  49. Hendrich B, Bird A (1998) Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 18:6538–6547PubMedGoogle Scholar
  50. Hermann A, Schmitt S, Jeltsch A (2003) The human Dnmt2 has residual DNA-(cytosine-C5) methyltransferase activity. J Biol Chem 278:31717–31721PubMedCrossRefGoogle Scholar
  51. Hiratani I, Gilbert DM (2009) Replication timing as an epigenetic mark. Epigenetics 4:93–97PubMedCrossRefGoogle Scholar
  52. Holm TM, Jackson-Grusby L, Brambrink T, Yamada Y, Rideout WM 3rd, Jaenisch R (2005) Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell 8:275–285PubMedCrossRefGoogle Scholar
  53. Howard G, Eiges R, Gaudet F, Jaenisch R, Eden A (2008) Activation and transposition of endogenous retroviral elements in hypomethylation induced tumors in mice. Oncogene 27:404–408PubMedCrossRefGoogle Scholar
  54. Hu N, Qiu X, Luo Y, Yuan J, Li Y, Lei W, Zhang G, Zhou Y, Su Y, Lu Q (2008) Abnormal histone modification patterns in lupus CD4+ T cells. J Rheumatol 35:804–810PubMedGoogle Scholar
  55. Huang YW, Liu JC, Deatherage DE, Luo J, Mutch DG, Goodfellow PJ, Miller DS, Huang TH (2009) Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer. Cancer Res 69:9038–9046PubMedCrossRefGoogle Scholar
  56. Huertas D, Sendra R, Munoz P (2009) Chromatin dynamics coupled to DNA repair. Epigenetics 4:31–42PubMedCrossRefGoogle Scholar
  57. Hurd PJ, Bannister AJ, Halls K, Dawson MA, Vermeulen M, Olsen JV, Ismail H, Somers J, Mann M, Owen-Hughes T et al (2009) Phosphorylation of histone H3 Thr-45 is linked to apoptosis. J Biol Chem 284:16575–16583PubMedCrossRefGoogle Scholar
  58. Illingworth RS, Bird AP (2009) CpG islands–‘a rough guide’. FEBS Lett 583:1713–1720PubMedCrossRefGoogle Scholar
  59. Jacinto FV, Esteller M (2007) MGMT hypermethylation: a prognostic foe, a predictive friend. DNA Repair (Amst) 6:1155–1160CrossRefGoogle Scholar
  60. Januchowski R, Wudarski M, Chwalinska-Sadowska H, Jagodzinski PP (2008) Prevalence of ZAP-70, LAT, SLP-76, and DNA methyltransferase 1 expression in CD4+ T cells of patients with systemic lupus erythematosus. Clin Rheumatol 27:21–27PubMedCrossRefGoogle Scholar
  61. Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J, Berdasco M, Fraga MF, O’Hanlon TP, Rider LG et al (2010) Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res 20:170–179PubMedCrossRefGoogle Scholar
  62. Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128:683–692PubMedCrossRefGoogle Scholar
  63. Karpf AR, Matsui S (2005) Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells. Cancer Res 65:8635–8639PubMedCrossRefGoogle Scholar
  64. Klose RJ, Bird AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31:89–97PubMedCrossRefGoogle Scholar
  65. Konkel MK, Batzer MA (2010) A mobile threat to genome stability: The impact of non-LTR retrotransposons upon the human genome. Semin Cancer Biol 20:211–221PubMedCrossRefGoogle Scholar
  66. Kuroda A, Rauch TA, Todorov I, Ku HT, Al-Abdullah IH, Kandeel F, Mullen Y, Pfeifer GP, Ferreri K (2009) Insulin gene expression is regulated by DNA methylation. PLoS One 4:e6953PubMedCrossRefGoogle Scholar
  67. Li Y, Zhao M, Yin H, Gao F, Wu X, Luo Y, Zhao S, Zhang X, Su Y, Hu N et al (2010) Overexpression of the growth arrest and DNA damage-induced 45alpha gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells. Arthritis Rheum 62:1438–1447PubMedCrossRefGoogle Scholar
  68. Liakopoulos V, Georgianos PI, Eleftheriadis T, Sarafidis PA (2011) Epigenetic mechanisms and kidney diseases. Curr Med Chem 18:1733–1739PubMedCrossRefGoogle Scholar
  69. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773PubMedCrossRefGoogle Scholar
  70. Liu H, Liu W, Wu Y, Zhou Y, Xue R, Luo C, Wang L, Zhao W, Jiang JD, Liu J (2005) Loss of epigenetic control of synuclein-gamma gene as a molecular indicator of metastasis in a wide range of human cancers. Cancer Res 65:7635–7643PubMedGoogle Scholar
  71. Maiwald R, Bonte A, Jung H, Bitter P, Storm Z, Laccone F, Herkenrath P (2002) De novo MECP2 mutation in a 46, XX male patient with Rett syndrome. Neurogenetics 4:107–108PubMedCrossRefGoogle Scholar
  72. Martin C, Zhang Y (2005) The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 6:838–849PubMedCrossRefGoogle Scholar
  73. Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D (1995) 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1:686–692PubMedCrossRefGoogle Scholar
  74. Miremadi A, Oestergaard MZ, Pharoah PD, Caldas C (2007) Cancer genetics of epigenetic genes. Hum Mol Genet 16(1):R28–R49PubMedCrossRefGoogle Scholar
  75. Mishra N, Brown DR, Olorenshaw IM, Kammer GM (2001) Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-gamma gene and protein expression in lupus T cells. Proc Natl Acad Sci USA 98:2628–2633PubMedCrossRefGoogle Scholar
  76. Mohandas T, Sparkes RS, Shapiro LJ (1981) Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation. Science 211:393–396PubMedCrossRefGoogle Scholar
  77. Mohn F, Schubeler D (2009) Genetics and epigenetics: stability and plasticity during cellular differentiation. Trends Genet 25:129–136PubMedCrossRefGoogle Scholar
  78. Nan X, Campoy FJ, Bird A (1997) MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell 88:471–481PubMedCrossRefGoogle Scholar
  79. Nan X, Meehan RR, Bird A (1993) Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res 21:4886–4892PubMedCrossRefGoogle Scholar
  80. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386–389PubMedCrossRefGoogle Scholar
  81. Nan X, Tate P, Li E, Bird A (1996) DNA methylation specifies chromosomal localization of MeCP2. Mol Cell Biol 16:414–421PubMedGoogle Scholar
  82. Nelson WG, De Marzo AM, Yegnasubramanian S (2009) Epigenetic alterations in human prostate cancers. Endocrinology 150:3991–4002PubMedCrossRefGoogle Scholar
  83. Ng SS, Yue WW, Oppermann U, Klose RJ (2009) Dynamic protein methylation in chromatin biology. Cell Mol Life Sci 66:407–422PubMedCrossRefGoogle Scholar
  84. Nishigaki M, Aoyagi K, Danjoh I, Fukaya M, Yanagihara K, Sakamoto H, Yoshida T, Sasaki H (2005) Discovery of aberrant expression of R-RAS by cancer-linked DNA hypomethylation in gastric cancer using microarrays. Cancer Res 65:2115–2124PubMedCrossRefGoogle Scholar
  85. Nowell PC (1989) The clonal nature of neoplasia. Cancer Cells 1:29–30PubMedGoogle Scholar
  86. Ogawa O, Eccles MR, Szeto J, McNoe LA, Yun K, Maw MA, Smith PJ, Reeve AE (1993) Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms’ tumour. Nature 362:749–751PubMedCrossRefGoogle Scholar
  87. Ordovas JM, Smith CE (2010) Epigenetics and cardiovascular disease. Nat Rev Cardiol 7:510–519PubMedCrossRefGoogle Scholar
  88. Oshimo Y, Nakayama H, Ito R, Kitadai Y, Yoshida K, Chayama K, Yasui W (2003) Promoter methylation of cyclin D2 gene in gastric carcinoma. Int J Oncol 23:1663–1670PubMedGoogle Scholar
  89. Pan W, Zhu S, Yuan M, Cui H, Wang L, Luo X, Li J, Zhou H, Tang Y, Shen N (2010) MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol 184:6773–6781PubMedCrossRefGoogle Scholar
  90. Paredes J, Albergaria A, Oliveira JT, Jeronimo C, Milanezi F, Schmitt FC (2005) P-cadherin overexpression is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation. Clin Cancer Res 11:5869–5877PubMedCrossRefGoogle Scholar
  91. Pedersen MT, Helin K (2010) Histone demethylases in development and disease. Trends Cell Biol 20:662–671PubMedCrossRefGoogle Scholar
  92. Portela A, Esteller M (2010) Epigenetic modifications and human disease. Nat Biotechnol 28:1057–1068PubMedCrossRefGoogle Scholar
  93. Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939PubMedCrossRefGoogle Scholar
  94. Rainier S, Johnson LA, Dobry CJ, Ping AJ, Grundy PE, Feinberg AP (1993) Relaxation of imprinted genes in human cancer. Nature 362:747–749PubMedCrossRefGoogle Scholar
  95. Richardson B (2003) DNA methylation and autoimmune disease. Clin Immunol 109:72–79PubMedCrossRefGoogle Scholar
  96. Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M (1990) Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 33:1665–1673PubMedCrossRefGoogle Scholar
  97. Roh TY, Wei G, Farrell CM, Zhao K (2007) Genome-wide prediction of conserved and nonconserved enhancers by histone acetylation patterns. Genome Res 17:74–81PubMedCrossRefGoogle Scholar
  98. Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, Jones PA (2006) Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 9:435–443PubMedCrossRefGoogle Scholar
  99. Schickel R, Boyerinas B, Park SM, Peter ME (2008) MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27:5959–5974PubMedCrossRefGoogle Scholar
  100. Schulz WA, Steinhoff C, Florl AR (2006) Methylation of endogenous human retroelements in health and disease. Curr Top Microbiol Immunol 310:211–250PubMedCrossRefGoogle Scholar
  101. Shirodkar AV, Marsden PA (2011) Epigenetics in cardiovascular disease. Curr Opin Cardiol 26:209–215PubMedCrossRefGoogle Scholar
  102. Skene PJ, Illingworth RS, Webb S, Kerr AR, James KD, Turner DJ, Andrews R, Bird AP (2010) Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell 37:457–468PubMedCrossRefGoogle Scholar
  103. Smeets E, Terhal P, Casaer P, Peters A, Midro A, Schollen E, van Roozendaal K, Moog U, Matthijs G, Herbergs J et al (2005) Rett syndrome in females with CTS hot spot deletions: a disorder profile. Am J Med Genet A 132A:117–120PubMedCrossRefGoogle Scholar
  104. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45PubMedCrossRefGoogle Scholar
  105. Straussman R, Nejman D, Roberts D, Steinfeld I, Blum B, Benvenisty N, Simon I, Yakhini Z, Cedar H (2009) Developmental programming of CpG island methylation profiles in the human genome. Nat Struct Mol Biol 16:564–571PubMedCrossRefGoogle Scholar
  106. Sullivan KE, Suriano A, Dietzmann K, Lin J, Goldman D, Petri MA (2007) The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus. Clin Immunol 123:74–81PubMedCrossRefGoogle Scholar
  107. Trojer P, Reinberg D (2007) Facultative heterochromatin: is there a distinctive molecular signature? Mol Cell 28:1–13PubMedCrossRefGoogle Scholar
  108. Tudor M, Akbarian S, Chen RZ, Jaenisch R (2002) Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain. Proc Natl Acad Sci USA 99:15536–15541PubMedCrossRefGoogle Scholar
  109. van Bavel CC, Dieker J, Muller S, Briand JP, Monestier M, Berden JH, van der Vlag J (2009) Apoptosis-associated acetylation on histone H2B is an epitope for lupus autoantibodies. Mol Immunol 47:511–516PubMedCrossRefGoogle Scholar
  110. van Bavel CC, Dieker JW, Kroeze Y, Tamboer WP, Voll R, Muller S, Berden JH, van der Vlag J (2011) Apoptosis-induced histone H3 methylation is targeted by autoantibodies in systemic lupus erythematosus. Ann Rheum Dis 70:201–207PubMedCrossRefGoogle Scholar
  111. Verdone L, Caserta M, Di Mauro E (2005) Role of histone acetylation in the control of gene expression. Biochem Cell Biol 83:344–353PubMedCrossRefGoogle Scholar
  112. Waddington CH (1942) The Epigenotpye. Endeavour pp. 18–20PubMedCrossRefGoogle Scholar
  113. Wang Z, Zang C, Cui K, Schones DE, Barski A, Peng W, Zhao K (2009) Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138:1019–1031PubMedCrossRefGoogle Scholar
  114. Watt F, Molloy PL (1988) Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev 2:1136–1143PubMedCrossRefGoogle Scholar
  115. Wilson AS, Power BE, Molloy PL (2007) DNA hypomethylation and human diseases. Biochim Biophys Acta 1775:138–162PubMedGoogle Scholar
  116. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, Song E (2007) Let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131:1109–1123PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of AnatomyUniversity of California San FranciscoSan FranciscoUSA

Personalised recommendations