Cellular and Molecular Life Sciences

, Volume 70, Issue 9, pp 1543–1573 | Cite as

The role of genetics in the establishment and maintenance of the epigenome

  • Covadonga Huidobro
  • Agustin F. Fernandez
  • Mario F. FragaEmail author
Multi-author review


Epigenetic mechanisms play an important role in gene regulation during development. DNA methylation, which is probably the most important and best-studied epigenetic mechanism, can be abnormally regulated in common pathologies, but the origin of altered DNA methylation remains unknown. Recent research suggests that these epigenetic alterations could depend, at least in part, on genetic mutations or polymorphisms in DNA methyltransferases and certain genes encoding enzymes of the one-carbon metabolism pathway. Indeed, the de novo methyltransferase 3B (DNMT3B) has been recently found to be mutated in several types of cancer and in the immunodeficiency, centromeric region instability and facial anomalies syndrome (ICF), in which these mutations could be related to the loss of global DNA methylation. In addition, mutations in glycine-N-methyltransferase (GNMT) could be associated with a higher risk of hepatocellular carcinoma and liver disease due to an unbalanced S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio, which leads to aberrant methylation reactions. Also, genetic variants of chromatin remodeling proteins and histone tail modifiers are involved in genetic disorders like α thalassemia X-linked mental retardation syndrome, CHARGE syndrome, Cockayne syndrome, Rett syndrome, systemic lupus erythematous, Rubinstein–Taybi syndrome, Coffin–Lowry syndrome, Sotos syndrome, and facioescapulohumeral syndrome, among others. Here, we review the potential genetic alterations with a possible role on epigenetic factors and discuss their contribution to human disease.


Epigenetics Mutation Disease 



We thank OIB (FYCIT) for editorial assistance. This work has been financially supported by FIS (FI07/00380 to C·H.); the FIS/FEDER (PI11/01728) and the ISCIII (CP11/00131) (to A.F·F.); the Spanish Ministry of Health (PI061267; PS09/02454 to M.F·F.); the Spanish National Research Council (CSIC; 200820I172 to M.F·F.); the Community of Asturias (FYCIT IB09-106 to M.F·F.). The IUOPA is supported by the Obra Social Cajastur, Spain.


  1. 1.
    Aapola U, Liiv I, Peterson P (2002) Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity. Nucleic Acids Res 30:3602–3608PubMedGoogle Scholar
  2. 2.
    Abidi F, Schwartz CE, Carpenter NJ, Villard L, Fontes M, Curtis M (1999) Carpenter-Waziri syndrome results from a mutation in XNP. Am J Med Genet 85:249–251PubMedGoogle Scholar
  3. 3.
    Abidi FE, Cardoso C, Lossi AM, Lowry RB, Depetris D, Mattei MG, Lubs HA, Stevenson RE, Fontes M, Chudley AE, Schwartz CE (2005) Mutation in the 5′ alternatively spliced region of the XNP/ATR-X gene causes Chudley-Lowry syndrome. Eur J Hum Genet 13:176–183PubMedGoogle Scholar
  4. 4.
    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 23:185–188PubMedGoogle Scholar
  5. 5.
    Anca MH, Gazit E, Loewenthal R, Ostrovsky O, Frydman M, Giladi N (2004) Different phenotypic expression in monozygotic twins with Huntington disease. Am J Med Genet A 124A:89–91PubMedGoogle Scholar
  6. 6.
    Anderson AN, Roncaroli F, Hodges A, Deprez M, Turkheimer FE (2008) Chromosomal profiles of gene expression in Huntington’s disease. Brain 131:381–388PubMedGoogle Scholar
  7. 7.
    Argentaro A, Yang JC, Chapman L, Kowalczyk MS, Gibbons RJ, Higgs DR, Neuhaus D, Rhodes D (2007) Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX. Proc Natl Acad Sci USA 104:11939–11944PubMedGoogle Scholar
  8. 8.
    Arrington CB, Cowley BC, Nightingale DR, Zhou H, Brothman AR, Viskochil DH (2005) Interstitial deletion 8q11.2-q13 with congenital anomalies of CHARGE association. Am J Med Genet A 133A:326–330PubMedGoogle Scholar
  9. 9.
    Augoustides-Savvopoulou P, Luka Z, Karyda S, Stabler SP, Allen RH, Patsiaoura K, Wagner C, Mudd SH (2003) Glycine N -methyltransferase deficiency: a new patient with a novel mutation. J Inherit Metab Dis 26:745–759PubMedGoogle Scholar
  10. 10.
    Aung PP, Matsumura S, Kuraoka K, Kunimitsu K, Yoshida K, Matsusaki K, Nakayama H, Yasui W (2005) No evidence of correlation between the single-nucleotide polymorphism of DNMT3B promoter and gastric cancer risk in a Japanese population. Oncol Rep 14:1151–1154PubMedGoogle Scholar
  11. 11.
    Avila MA, Berasain C, Torres L, Martin-Duce A, Corrales FJ, Yang H, Prieto J, Lu SC, Caballeria J, Rodes J, Mato JM (2000) Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma. J Hepatol 33:907–914PubMedGoogle Scholar
  12. 12.
    Bajpai R, Chen DA, Rada-Iglesias A, Zhang J, Xiong Y, Helms J, Chang CP, Zhao Y, Swigut T, Wysocka J (2010) CHD7 cooperates with PBAF to control multipotent neural crest formation. Nature 463:958–962PubMedGoogle Scholar
  13. 13.
    Balaghi M, Horne DW, Wagner C (1993) Hepatic one-carbon metabolism in early folate deficiency in rats. Biochem J 291(Pt 1):145–149PubMedGoogle Scholar
  14. 14.
    Balding DJ (2006) A tutorial on statistical methods for population association studies. Nat Rev Genet 7:781–791PubMedGoogle Scholar
  15. 15.
    Ballestar E, Esteller M, Richardson BC (2006) The epigenetic face of systemic lupus erythematosus. J Immunol 176:7143–7147PubMedGoogle Scholar
  16. 16.
    Bao Q, He B, Pan Y, Tang Z, Zhang Y, Qu L, Xu Y, Zhu C, Tian F, Wang S (2011) Genetic variation in the promoter of DNMT3B is associated with the risk of colorectal cancer. Int J Colorectal Dis 26:1107–1112PubMedGoogle Scholar
  17. 17.
    Baric I (2009) Inherited disorders in the conversion of methionine to homocysteine. J Inherit Metab Dis 32:459–471PubMedGoogle Scholar
  18. 18.
    Bashtrykov P, Jankevicius G, Smarandache A, Jurkowska RZ, Ragozin S, Jeltsch A (2012) Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain. Chem Biol 19:572–578PubMedGoogle Scholar
  19. 19.
    Baujat G, Cormier-Daire V (2007) Sotos syndrome. Orphanet J Rare Dis 2:36PubMedGoogle Scholar
  20. 20.
    Beaulieu N, Morin S, Chute IC, Robert MF, Nguyen H, MacLeod AR (2002) An essential role for DNA methyltransferase DNMT3B in cancer cell survival. J Biol Chem 277:28176–28181PubMedGoogle Scholar
  21. 21.
    Beerens N, Hoeijmakers JH, Kanaar R, Vermeulen W, Wyman C (2005) The CSB protein actively wraps DNA. J Biol Chem 280:4722–4729PubMedGoogle Scholar
  22. 22.
    Bergman JE, Janssen N, Hoefsloot LH, Jongmans MC, Hofstra RM, van Ravenswaaij-Arts CM (2011) CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype. J Med Genet 48:334–342PubMedGoogle Scholar
  23. 23.
    Berube NG, Smeenk CA, Picketts DJ (2000) Cell cycle-dependent phosphorylation of the ATRX protein correlates with changes in nuclear matrix and chromatin association. Hum Mol Genet 9:539–547PubMedGoogle Scholar
  24. 24.
    Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9:2395–2402PubMedGoogle Scholar
  25. 25.
    Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B (1999) Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 59:74–79PubMedGoogle Scholar
  26. 26.
    Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21PubMedGoogle Scholar
  27. 27.
    Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekstrom TJ, Harris TB, Launer LJ, Eiriksdottir G, Leppert MF, Sapienza C, Gudnason V, Feinberg AP (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299:2877–2883PubMedGoogle Scholar
  28. 28.
    Blasco MA (2007) The epigenetic regulation of mammalian telomeres. Nat Rev Genet 8:299–309PubMedGoogle Scholar
  29. 29.
    Bodega B, Ramirez GD, Grasser F, Cheli S, Brunelli S, Mora M, Meneveri R, Marozzi A, Mueller S, Battaglioli E, Ginelli E (2009) Remodeling of the chromatin structure of the facioscapulohumeral muscular dystrophy (FSHD) locus and upregulation of FSHD-related gene 1 (FRG1) expression during human myogenic differentiation. BMC Biol 7:41PubMedGoogle Scholar
  30. 30.
    Bosman EA, Penn AC, Ambrose JC, Kettleborough R, Stemple DL, Steel KP (2005) Multiple mutations in mouse Chd7 provide models for CHARGE syndrome. Hum Mol Genet 14:3463–3476PubMedGoogle Scholar
  31. 31.
    Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH (2001) Dnmt3L and the establishment of maternal genomic imprints. Science 294:2536–2539PubMedGoogle Scholar
  32. 32.
    Cabianca DS, Casa V, Bodega B, Xynos A, Ginelli E, Tanaka Y, Gabellini D (2012) A long ncRNA links copy number variation to a Polycomb/trithorax epigenetic switch in FSHD muscular dystrophy. Cell 149:819–831PubMedGoogle Scholar
  33. 33.
    Cabianca DS, Gabellini D (2010) The cell biology of disease: FSHD: copy number variations on the theme of muscular dystrophy. J Cell Biol 191:1049–1060PubMedGoogle Scholar
  34. 34.
    Cacurri S, Piazzo N, Deidda G, Vigneti E, Galluzzi G, Colantoni L, Merico B, Ricci E, Felicetti L (1998) Sequence homology between 4qter and 10qter loci facilitates the instability of subtelomeric KpnI repeat units implicated in facioscapulohumeral muscular dystrophy. Am J Hum Genet 63:181–190PubMedGoogle Scholar
  35. 35.
    Cai J, Mao Z, Hwang JJ, Lu SC (1998) Differential expression of methionine adenosyltransferase genes influences the rate of growth of human hepatocellular carcinoma cells. Cancer Res 58:1444–1450PubMedGoogle Scholar
  36. 36.
    Cai J, Sun WM, Hwang JJ, Stain SC, Lu SC (1996) Changes in S-adenosylmethionine synthetase in human liver cancer: molecular characterization and significance. Hepatology 24:1090–1097PubMedGoogle Scholar
  37. 37.
    Cano A, Buqué X, Martínez-Uña M, Aurrekoetxea I, Menor A, García-Rodriguez JL, Lu SC, Martínez-Chantar M, Mato JM, Ochoa B, Aspichueta P (2011) Methionine adenosyltransferase 1A gene deletion disrupts hepatic VLDL assembly in mice. Hepatology doi: 10.1002/hep.24607. (epub ahead of print)
  38. 38.
    Caramel J, Quignon F, Delattre O (2008) RhoA-dependent regulation of cell migration by the tumor suppressor hSNF5/INI1. Cancer Res 68:6154–6161PubMedGoogle Scholar
  39. 39.
    Cardoso C, Lutz Y, Mignon C, Compe E, Depetris D, Mattei MG, Fontes M, Colleaux L (2000) ATR-X mutations cause impaired nuclear location and altered DNA binding properties of the XNP/ATR-X protein. J Med Genet 37:746–751PubMedGoogle Scholar
  40. 40.
    Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontes M, Colleaux L (1998) Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein. Hum Mol Genet 7:679–684PubMedGoogle Scholar
  41. 41.
    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 320:1224–1229PubMedGoogle Scholar
  42. 42.
    Chahrour M, Zoghbi HY (2007) The story of Rett syndrome: from clinic to neurobiology. Neuron 56:422–437PubMedGoogle Scholar
  43. 43.
    Chan HM, La Thangue NB (2001) p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci 114:2363–2373PubMedGoogle Scholar
  44. 44.
    Chang KP, Hao SP, Liu CT, Cheng MH, Chang YL, Lee YS, Wang TH, Tsai CN (2007) Promoter polymorphisms of DNMT3B and the risk of head and neck squamous cell carcinoma in Taiwan: a case-control study. Oral Oncol 43:345–351PubMedGoogle Scholar
  45. 45.
    Chang KP, Hao SP, Tsang NM, Chang YL, Cheng MH, Liu CT, Lee YS, Tsai CL, Lee TJ, Wang TH, Tsai CN (2008) Gene expression and promoter polymorphisms of DNA methyltransferase 3B in nasopharyngeal carcinomas in Taiwanese people: a case-control study. Oncol Rep 19:217–222PubMedGoogle Scholar
  46. 46.
    Chen CP, Lin SP, Chang TY, Chiu NC, Shih SL, Lin CJ, Wang W, Hsu HC (2002) Perinatal imaging findings of inherited Sotos syndrome. Prenat Diagn 22:887–892PubMedGoogle Scholar
  47. 47.
    Chen L, Zeng Y, Yang H, Lee TD, French SW, Corrales FJ, Garcia-Trevijano ER, Avila MA, Mato JM, Lu SC (2004) Impaired liver regeneration in mice lacking methionine adenosyltransferase 1A. FASEB J 18:914–916PubMedGoogle Scholar
  48. 48.
    Chen SY, Lin JR, Darbha R, Lin P, Liu TY, Chen YM (2004) Glycine N-methyltransferase tumor susceptibility gene in the benzo(a)pyrene-detoxification pathway. Cancer Res 64:3617–3623PubMedGoogle Scholar
  49. 49.
    Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC, Jaenisch R, Greenberg ME (2003) Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302:885–889PubMedGoogle Scholar
  50. 50.
    Chen YM, Chen LY, Wong FH, Lee CM, Chang TJ, Yang-Feng TL (2000) Genomic structure, expression, and chromosomal localization of the human glycine N-methyltransferase gene. Genomics 66:43–47PubMedGoogle Scholar
  51. 51.
    Chen YM, Liao YJ, Liu SP, Tsai TF (2009) Phenotypic differences between two Gnmt−/− mouse models for hepatocellular carcinoma. Hepatology 49:2130–2131 (author reply 2131)PubMedGoogle Scholar
  52. 52.
    Cho YY, Yao K, Pugliese A, Malakhova ML, Bode AM, Dong Z (2009) A regulatory mechanism for RSK2 NH(2)-terminal kinase activity. Cancer Res 69:4398–4406PubMedGoogle Scholar
  53. 53.
    Citterio E, Van Den Boom V, Schnitzler G, Kanaar R, Bonte E, Kingston RE, Hoeijmakers JH, Vermeulen W (2000) ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor. Mol Cell Biol 20:7643–7653PubMedGoogle Scholar
  54. 54.
    Clark DE, Errington TM, Smith JA, Frierson HF Jr, Weber MJ, Lannigan DA (2005) The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferation. Cancer Res 65:3108–3116PubMedGoogle Scholar
  55. 55.
    Cohen DR, Matarazzo V, Palmer AM, Tu Y, Jeon OH, Pevsner J, Ronnett GV (2003) Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis. Mol Cell Neurosci 22:417–429PubMedGoogle Scholar
  56. 56.
    Collins AL, Levenson JM, Vilaythong AP, Richman R, Armstrong DL, Noebels JL, David Sweatt J, Zoghbi HY (2004) Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 13:2679–2689PubMedGoogle Scholar
  57. 57.
    Cook RJ, Wagner C (1984) Glycine N-methyltransferase is a folate binding protein of rat liver cytosol. Proc Natl Acad Sci USA 81:3631–3634PubMedGoogle Scholar
  58. 58.
    Couce ML, Boveda MD, Castineiras DE, Corrales FJ, Mora MI, Fraga JM, Mudd SH (2008) Hypermethioninaemia due to methionine adenosyltransferase I/III (MAT I/III) deficiency: diagnosis in an expanded neonatal screening programme. J Inherit Metab Dis 31(Suppl 2):233–239Google Scholar
  59. 59.
    Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90:537–548PubMedGoogle Scholar
  60. 60.
    Daxinger L, Whitelaw E (2011) Transgenerational epigenetic inheritance: more questions than answers. Genome Res 20:1623–1628Google Scholar
  61. 61.
    De Cesare D, Jacquot S, Hanauer A, Sassone-Corsi P (1998) Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene. Proc Natl Acad Sci USA 95:12202–12207PubMedGoogle Scholar
  62. 62.
    de Greef JC, Lemmers RJ, van Engelen BG, Sacconi S, Venance SL, Frants RR, Tawil R, van der Maarel SM (2009) Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. Hum Mutat 30:1449–1459PubMedGoogle Scholar
  63. 63.
    Debacker K, Frizzell A, Gleeson O, Kirkham-McCarthy L, Mertz T, Lahue RS (2012) Histone deacetylase complexes promote trinucleotide repeat expansions. Plos Biol 10:1001257Google Scholar
  64. 64.
    DelBove J, Kuwahara Y, Mora-Blanco EL, Godfrey V, Funkhouser WK, Fletcher CD, Van Dyke T, Roberts CW, Weissman BE (2009) Inactivation of SNF5 cooperates with p53 loss to accelerate tumor formation in Snf5(±);p53(±) mice. Mol Carcinog 48:1139–1148PubMedGoogle Scholar
  65. 65.
    Deng C, Kaplan MJ, Yang J, Ray D, Zhang Z, McCune WJ, Hanash SM, Richardson BC (2001) Decreased Ras-mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients. Arthritis Rheum 44:397–407PubMedGoogle Scholar
  66. 66.
    Deng Z, Campbell AE, Lieberman PM (2010) TERRA, CpG methylation and telomere heterochromatin: lessons from ICF syndrome cells. Cell Cycle 9:69–74PubMedGoogle Scholar
  67. 67.
    Deng Z, Norseen J, Wiedmer A, Riethman H, Lieberman PM (2009) TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Mol Cell 35:403–413PubMedGoogle Scholar
  68. 68.
    Denissenko MF, Chen JX, Tang MS, Pfeifer GP (1997) Cytosine methylation determines hot spots of DNA damage in the human P53 gene. Proc Natl Acad Sci USA 94:3893–3898PubMedGoogle Scholar
  69. 69.
    Dhayalan A, Tamas R, Bock I, Tattermusch A, Dimitrova E, Kudithipudi S, Ragozin S, Jeltsch A (2011) The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9. Hum Mol Genet 20:2195–2203PubMedGoogle Scholar
  70. 70.
    DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277:1990–1993PubMedGoogle Scholar
  71. 71.
    Dixit M, Ansseau E, Tassin A, Winokur S, Shi R, Qian H, Sauvage S, Matteotti C, van Acker AM, Leo O, Figlewicz D, Barro M, Laoudj-Chenivesse D, Belayew A, Coppee F, Chen YW (2007) DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1. Proc Natl Acad Sci USA 104:18157–18162PubMedGoogle Scholar
  72. 72.
    Dolinoy DC (2008) The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev 66(Suppl 1):S7–S11PubMedGoogle Scholar
  73. 73.
    Dugani CB, Paquin A, Kaplan DR, Miller FD (2010) Coffin-Lowry syndrome: a role for RSK2 in mammalian neurogenesis. Dev Biol 347:348–359PubMedGoogle Scholar
  74. 74.
    Duhl DM, Vrieling H, Miller KA, Wolff GL, Barsh GS (1994) Neomorphic agouti mutations in obese yellow mice. Nat Genet 8:59–65PubMedGoogle Scholar
  75. 75.
    Duthie SJ (1999) Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull 55:578–592PubMedGoogle Scholar
  76. 76.
    Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M, Folstein S, Ross C, Franz M, Abbott M et al (1993) Trinucleotide repeat length instability and age of onset in Huntington’s disease. Nat Genet 4:387–392PubMedGoogle Scholar
  77. 77.
    Eckhardt F, Lewin J, Cortese R, Rakyan VK, Attwood J, Burger M, Burton J, Cox TV, Davies R, Down TA, Haefliger C, Horton R, Howe K, Jackson DK, Kunde J, Koenig C, Liddle J, Niblett D, Otto T, Pettett R, Seemann S, Thompson C, West T, Rogers J, Olek A, Berlin K, Beck S (2006) DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet 38:1378–1385PubMedGoogle Scholar
  78. 78.
    Ehrlich M (2003) The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease. Clin Immunol 109:17–28PubMedGoogle Scholar
  79. 79.
    Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, Gehrke C (1982) Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res 10:2709–2721PubMedGoogle Scholar
  80. 80.
    Ehrlich M, Sanchez C, Shao C, Nishiyama R, Kehrl J, Kuick R, Kubota T, Hanash SM (2008) ICF, an immunodeficiency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation. Autoimmunity 41:253–271PubMedGoogle Scholar
  81. 81.
    Ehrnhoefer DE, Sutton L, Hayden MR (2011) Small changes, big impact: posttranslational modifications and function of huntingtin in Huntington disease. Neuroscientist 17:475–492PubMedGoogle Scholar
  82. 82.
    El-Maarri O, Becker T, Junen J, Manzoor SS, Diaz-Lacava A, Schwaab R, Wienker T, Oldenburg J (2007) Gender specific differences in levels of DNA methylation at selected loci from human total blood: a tendency toward higher methylation levels in males. Hum Genet 122:505–514PubMedGoogle Scholar
  83. 83.
    El-Maarri O, Kareta MS, Mikeska T, Becker T, Diaz-Lacava A, Junen J, Nusgen N, Behne F, Wienker T, Waha A, Oldenburg J, Chedin F (2009) A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation. Hum Mol Genet 18:1755–1768PubMedGoogle Scholar
  84. 84.
    Ellis L, Atadja PW, Johnstone RW (2009) Epigenetics in cancer: targeting chromatin modifications. Mol Cancer Ther 8:1409–1420PubMedGoogle Scholar
  85. 85.
    Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298PubMedGoogle Scholar
  86. 86.
    Esteller M (2008) Epigenetics in cancer. N Engl J Med 358:1148–1159PubMedGoogle Scholar
  87. 87.
    Ezzikouri S, El Feydi AE, Benazzouz M, Afifi R, El Kihal L, Hassar M, Akil A, Pineau P, Benjelloun S (2009) Single-nucleotide polymorphism in DNMT3B promoter and its association with hepatocellular carcinoma in a Moroccan population. Infect Genet Evol 9:877–881PubMedGoogle Scholar
  88. 88.
    Fan H, Zhang F, Hu J, Liu D, Zhao Z (2008) Promoter polymorphisms of DNMT3B and the risk of colorectal cancer in Chinese: a case-control study. J Exp Clin Cancer Res 27:24PubMedGoogle Scholar
  89. 89.
    Feinberg AP (2010) Genome-scale approaches to the epigenetics of common human disease. Virchows Arch 456:13–21PubMedGoogle Scholar
  90. 90.
    Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4:143–153PubMedGoogle Scholar
  91. 91.
    Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92PubMedGoogle Scholar
  92. 92.
    Ferrante RJ, Kubilus JK, Lee J, Ryu H, Beesen A, Zucker B, Smith K, Kowall NW, Ratan RR, Luthi-Carter R, Hersch SM (2003) Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington’s disease mice. J Neurosci 23:9418–9427PubMedGoogle Scholar
  93. 93.
    Fischer M, Pereira PM, Holtmann B, Simon CM, Hanauer A, Heisenberg M, Sendtner M (2009) P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons. Mol Cell Neurosci 42:134–141PubMedGoogle Scholar
  94. 94.
    Flaus A, Martin DM, Barton GJ, Owen-Hughes T (2006) Identification of multiple distinct Snf2 subfamilies with conserved structural motifs. Nucleic Acids Res 34:2887–2905PubMedGoogle Scholar
  95. 95.
    Fong CB, Thong MK, Sam CK, Mohamed Noor MN, Ariffin R (2009) MECP2 mutations in Malaysian Rett syndrome patients. Singapore Med J 50:529–533PubMedGoogle Scholar
  96. 96.
    Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604–10609PubMedGoogle Scholar
  97. 97.
    Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG, Perez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MA, Ahn N, Imhof A, Caldas C, Jenuwein T, Esteller M (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37:391–400PubMedGoogle Scholar
  98. 98.
    Fraga MF, Esteller M (2005) Towards the human cancer epigenome: a first draft of histone modifications. Cell Cycle 4:1377–1381PubMedGoogle Scholar
  99. 99.
    Friedman JH, Trieschmann ME, Myers RH, Fernandez HH (2005) Monozygotic twins discordant for Huntington disease after 7 years. Arch Neurol 62:995–997PubMedGoogle Scholar
  100. 100.
    Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, Ogura C, Okazaki Y, Jinno Y (2004) Age-related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet 68:196–204PubMedGoogle Scholar
  101. 101.
    Gabellini D, D’Antona G, Moggio M, Prelle A, Zecca C, Adami R, Angeletti B, Ciscato P, Pellegrino MA, Bottinelli R, Green MR, Tupler R (2006) Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1. Nature 439:973–977PubMedGoogle Scholar
  102. 102.
    Gabellini D, Green MR, Tupler R (2002) Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle. Cell 110:339–348PubMedGoogle Scholar
  103. 103.
    Gallagher A, Hallahan B (2011) Fragile X-associated disorders: a clinical overview. J Neurol 259:401–413PubMedGoogle Scholar
  104. 104.
    Gardian G, Browne SE, Choi DK, Klivenyi P, Gregorio J, Kubilus JK, Ryu H, Langley B, Ratan RR, Ferrante RJ, Beal MF (2005) Neuroprotective effects of phenylbutyrate in the N171–82Q transgenic mouse model of Huntington’s disease. J Biol Chem 280:556–563PubMedGoogle Scholar
  105. 105.
    Garrick D, Sharpe JA, Arkell R, Dobbie L, Smith AJ, Wood WG, Higgs DR, Gibbons RJ (2006) Loss of Atrx affects trophoblast development and the pattern of X-inactivation in extraembryonic tissues. PLoS Genet 2:e58PubMedGoogle Scholar
  106. 106.
    Gatto S, Della Ragione F, Cimmino A, Strazzullo M, Fabbri M, Mutarelli M, Ferraro L, Weisz A, D’Esposito M, Matarazzo MR (2010) Epigenetic alteration of microRNAs in DNMT3B-mutated patients of ICF syndrome. Epigenetics 5:427–443PubMedGoogle Scholar
  107. 107.
    Gaull GE, Tallan HH (1974) Methionine adenosyltransferase deficiency: new enzymatic defect associated with hypermethioninemia. Science 186:59–60PubMedGoogle Scholar
  108. 108.
    Georgel PT, Horowitz-Scherer RA, Adkins N, Woodcock CL, Wade PA, Hansen JC (2003) Chromatin compaction by human MeCP2. Assembly of novel secondary chromatin structures in the absence of DNA methylation. J Biol Chem 278:32181–32188PubMedGoogle Scholar
  109. 109.
    Georgiou N, Bradshaw JL, Chiu E, Tudor A, O’Gorman L, Phillips JG (1999) Differential clinical and motor control function in a pair of monozygotic twins with Huntington’s disease. Mov Disord 14:320–325PubMedGoogle Scholar
  110. 110.
    Gervasini C, Castronovo P, Bentivegna A, Mottadelli F, Faravelli F, Giovannucci-Uzielli ML, Pessagno A, Lucci-Cordisco E, Pinto AM, Salviati L, Selicorni A, Tenconi R, Neri G, Larizza L (2007) High frequency of mosaic CREBBP deletions in Rubinstein-Taybi syndrome patients and mapping of somatic and germ-line breakpoints. Genomics 90:567–573PubMedGoogle Scholar
  111. 111.
    Gervasini C, Mottadelli F, Ciccone R, Castronovo P, Milani D, Scarano G, Bedeschi MF, Belli S, Pilotta A, Selicorni A, Zuffardi O, Larizza L (2010) High frequency of copy number imbalances in Rubinstein-Taybi patients negative to CREBBP mutational analysis. Eur J Hum Genet 18:768–775PubMedGoogle Scholar
  112. 112.
    Ghosh RP, Horowitz-Scherer RA, Nikitina T, Gierasch LM, Woodcock CL (2008) Rett syndrome-causing mutations in human MeCP2 result in diverse structural changes that impact folding and DNA interactions. J Biol Chem 283:20523–20534PubMedGoogle Scholar
  113. 113.
    Ghosh RP, Horowitz-Scherer RA, Nikitina T, Shlyakhtenko LS, Woodcock CL (2010) MeCP2 binds cooperatively to its substrate and competes with histone H1 for chromatin binding sites. Mol Cell Biol 30:4656–4670PubMedGoogle Scholar
  114. 114.
    Gibbons R (2006) Alpha thalassaemia-mental retardation. X linked. Orphanet J Rare Dis 1:15Google Scholar
  115. 115.
    Gibbons RJ, McDowell TL, Raman S, O’Rourke DM, Garrick D, Ayyub H, Higgs DR (2000) Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation. Nat Genet 24:368–371PubMedGoogle Scholar
  116. 116.
    Gibbons RJ, Picketts DJ, Villard L, Higgs DR (1995) Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell 80:837–845PubMedGoogle Scholar
  117. 117.
    Gibbons RJ, Suthers GK, Wilkie AO, Buckle VJ, Higgs DR (1992) X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis. Am J Hum Genet 51:1136–1149PubMedGoogle Scholar
  118. 118.
    Gibbons RJ, Wada T, Fisher CA, Malik N, Mitson MJ, Steensma DP, Fryer A, Goudie DR, Krantz ID, Traeger-Synodinos J (2008) Mutations in the chromatin-associated protein ATRX. Hum Mutat 29:796–802PubMedGoogle Scholar
  119. 119.
    Gibson JH, Slobedman B, NH K, Williamson SL, Minchenko D, El-Osta A, Stern JL, Christodoulou J (2010) Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain. BMC Neurosci 11:53PubMedGoogle Scholar
  120. 120.
    Gil B, Casado M, Pajares MA, Bosca L, Mato JM, Martin-Sanz P, Alvarez L (1996) Differential expression pattern of S-adenosylmethionine synthetase isoenzymes during rat liver development. Hepatology 24:876–881PubMedGoogle Scholar
  121. 121.
    Giordano A, Avantaggiati ML (1999) p300 and CBP: partners for life and death. J Cell Physiol 181:218–230PubMedGoogle Scholar
  122. 122.
    Gomez-Esteban JC, Lezcano E, Zarranz JJ, Velasco F, Garamendi I, Perez T, Tijero B (2007) Monozygotic twins suffering from Huntington’s disease show different cognitive and behavioural symptoms. Eur Neurol 57:26–30PubMedGoogle Scholar
  123. 123.
    Gonzalgo ML, Jones PA (1997) Mutagenic and epigenetic effects of DNA methylation. Mutat Res 386:107–118PubMedGoogle Scholar
  124. 124.
    Gourley M, Miller FW (2007) Mechanisms of disease: Environmental factors in the pathogenesis of rheumatic disease. Nat Clin Pract Rheumatol 3:172–180PubMedGoogle Scholar
  125. 125.
    Gowher H, Liebert K, Hermann A, Xu G, Jeltsch A (2005) Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. J Biol Chem 280:13341–13348PubMedGoogle Scholar
  126. 126.
    Goyal R, Reinhardt R, Jeltsch A (2006) Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase. Nucleic Acids Res 34:1182–1188PubMedGoogle Scholar
  127. 127.
    Group THsDCR (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983Google Scholar
  128. 128.
    Guidi CJ, Sands AT, Zambrowicz BP, Turner TK, Demers DA, Webster W, Smith TW, Imbalzano AN, Jones SN (2001) Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice. Mol Cell Biol 21:3598–3603PubMedGoogle Scholar
  129. 129.
    Guo X, Zhang L, Wu M, Wang N, Liu Y, Er L, Wang S, Gao Y, Yu W, Xue H, Xu Z (2010) Association of the DNMT3B polymorphism with colorectal adenomatous polyps and adenocarcinoma. Mol Biol Rep 37:219–225PubMedGoogle Scholar
  130. 130.
    Guy J, Gan J, Selfridge J, Cobb S, Bird A (2007) Reversal of neurological defects in a mouse model of Rett syndrome. Science 315:1143–1147PubMedGoogle Scholar
  131. 131.
    Hagerman RJ, Hagerman PJ (2002) The fragile X premutation: into the phenotypic fold. Curr Opin Genet Dev 12:278–283PubMedGoogle Scholar
  132. 132.
    Hagleitner MM, Lankester A, Maraschio P, Hulten M, Fryns JP, Schuetz C, Gimelli G, Davies EG, Gennery A, Belohradsky BH, de Groot R, Gerritsen EJ, Mattina T, Howard PJ, Fasth A, Reisli I, Furthner D, Slatter MA, Cant AJ, Cazzola G, van Dijken PJ, van Deuren M, de Greef JC, van der Maarel SM, Weemaes CM (2008) Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome). J Med Genet 45:93–99PubMedGoogle Scholar
  133. 133.
    Hanel ML, Sun CY, Jones TI, Long SW, Zanotti S, Milner D, Jones PL (2011) Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein. Differentiation 81:107–118PubMedGoogle Scholar
  134. 134.
    Hansen FJ, Friis B (1976) Familial occurrence of cerebral gigantism, Sotos’ syndrome. Acta Paediatr Scand 65:387–389PubMedGoogle Scholar
  135. 135.
    Hansen JC, Ghosh RP, Woodcock CL (2010) Binding of the Rett syndrome protein, MeCP2, to methylated and unmethylated DNA and chromatin. IUBMB Life 62:732–738PubMedGoogle Scholar
  136. 136.
    Hansen RS, Stoger R, Wijmenga C, Stanek AM, Canfield TK, Luo P, Matarazzo MR, D’Esposito M, Feil R, Gimelli G, Weemaes CM, Laird CD, Gartler SM (2000) Escape from gene silencing in ICF syndrome: evidence for advanced replication time as a major determinant. Hum Mol Genet 9:2575–2587PubMedGoogle Scholar
  137. 137.
    Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, Gartler SM (1999) The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc Natl Acad Sci USA 96:14412–14417PubMedGoogle Scholar
  138. 138.
    Hendrich B, Bird A (1998) Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 18:6538–6547PubMedGoogle Scholar
  139. 139.
    Hennekam RC (2006) Rubinstein-Taybi syndrome. Eur J Hum Genet 14:981–985PubMedGoogle Scholar
  140. 140.
    Herman JG (1999) Hypermethylation of tumor suppressor genes in cancer. Semin Cancer Biol 9:359–367PubMedGoogle Scholar
  141. 141.
    Hess JL (2004) MLL: a histone methyltransferase disrupted in leukemia. Trends Mol Med 10:500–507PubMedGoogle Scholar
  142. 142.
    Hockly E, Richon VM, Woodman B, Smith DL, Zhou X, Rosa E, Sathasivam K, Ghazi-Noori S, Mahal A, Lowden PA, Steffan JS, Marsh JL, Thompson LM, Lewis CM, Marks PA, Bates GP (2003) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc Natl Acad Sci USA 100:2041–2046PubMedGoogle Scholar
  143. 143.
    Hong YS, Lee HJ, You CH, Roh MS, Kwak JY, Lee MJ, Kim JY (2007) DNMT3b 39179GT polymorphism and the risk of adenocarcinoma of the colon in Koreans. Biochem Genet 45:155–163PubMedGoogle Scholar
  144. 144.
    Horibata K, Saijo M, Bay MN, Lan L, Kuraoka I, Brooks PJ, Honma M, Nohmi T, Yasui A, Tanaka K (2011) Mutant Cockayne syndrome group B protein inhibits repair of DNA topoisomerase I-DNA covalent complex. Genes Cells 16:101–114PubMedGoogle Scholar
  145. 145.
    Horikawa S, Tsukada K (1992) Molecular cloning and developmental expression of a human kidney S-adenosylmethionine synthetase. FEBS Lett 312:37–41PubMedGoogle Scholar
  146. 146.
    Horike S, Cai S, Miyano M, Cheng JF, Kohwi-Shigematsu T (2005) Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat Genet 37:31–40PubMedGoogle Scholar
  147. 147.
    Howard PJ, Lewis IJ, Harris F, Walker S (1985) Centromeric instability of chromosomes 1 and 16 with variable immune deficiency: a new syndrome. Clin Genet 27:501–505PubMedGoogle Scholar
  148. 148.
    Hu J, Fan H, Liu D, Zhang S, Zhang F, Xu H (2010) DNMT3B promoter polymorphism and risk of gastric cancer. Dig Dis Sci 55:1011–1016PubMedGoogle Scholar
  149. 149.
    Huang N, vom Baur E, Garnier JM, Lerouge T, Vonesch JL, Lutz Y, Chambon P, Losson R (1998) Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators. EMBO J 17:3398–3412PubMedGoogle Scholar
  150. 150.
    Hulten M (1978) Selective somatic pairing and fragility at 1q12 in a boy with common variable immunodeficiency: a new syndrome. Clin Genet 14:294Google Scholar
  151. 151.
    Huyhn K, Renfree MB, Graves JA, Pask AJ (2011) ATRX has a critical and conserved role in mammalian sexual differentiation. BMC Dev Biol 11:39PubMedGoogle Scholar
  152. 152.
    Isakoff MS, Sansam CG, Tamayo P, Subramanian A, Evans JA, Fillmore CM, Wang X, Biegel JA, Pomeroy SL, Mesirov JP, Roberts CW (2005) Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation. Proc Natl Acad Sci USA 102:17745–17750PubMedGoogle Scholar
  153. 153.
    Iwase S, Xiang B, Ghosh S, Ren T, Lewis PW, Cochrane JC, Allis CD, Picketts DJ, Patel DJ, Li H, Shi Y (2011) ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome. Nat Struct Mol Biol 18:769–776PubMedGoogle Scholar
  154. 154.
    Jacquot S, Zeniou M, Touraine R, Hanauer A (2002) X-linked Coffin-Lowry syndrome (CLS, MIM 303600, RPS6KA3 gene, protein product known under various names: pp 90(rsk2), RSK2, ISPK, MAPKAP1). Eur J Hum Genet 10:2–5PubMedGoogle Scholar
  155. 155.
    Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl):245–254PubMedGoogle Scholar
  156. 156.
    Jagani Z, Mora-Blanco EL, Sansam CG, McKenna ES, Wilson B, Chen D, Klekota J, Tamayo P, Nguyen PT, Tolstorukov M, Park PJ, Cho YJ, Hsiao K, Buonamici S, Pomeroy SL, Mesirov JP, Ruffner H, Bouwmeester T, Luchansky SJ, Murtie J, Kelleher JF, Warmuth M, Sellers WR, Roberts CW, Dorsch M (2010) Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway. Nat Med 16:1429–1433PubMedGoogle Scholar
  157. 157.
    Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J, Berdasco M, Fraga MF, O’Hanlon TP, Rider LG, Jacinto FV, Lopez-Longo FJ, Dopazo J, Forn M, Peinado MA, Carreno L, Sawalha AH, Harley JB, Siebert R, Esteller M, Miller FW, Ballestar E (2010) Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res 20:170–179PubMedGoogle Scholar
  158. 158.
    Jeanpierre M, Turleau C, Aurias A, Prieur M, Ledeist F, Fischer A, Viegas-Pequignot E (1993) An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome. Hum Mol Genet 2:731–735PubMedGoogle Scholar
  159. 159.
    Jefferson A, Colella S, Moralli D, Wilson N, Yusuf M, Gimelli G, Ragoussis J, Volpi EV (2010) Altered intra-nuclear organisation of heterochromatin and genes in ICF syndrome. PLoS One 5:e11364PubMedGoogle Scholar
  160. 160.
    Jiang YL, Rigolet M, Bourc’his D, Nigon F, Bokesoy I, Fryns JP, Hulten M, Jonveaux P, Maraschio P, Megarbane A, Moncla A, Viegas-Pequignot E (2005) DNMT3B mutations and DNA methylation defect define two types of ICF syndrome. Hum Mutat 25:56–63PubMedGoogle Scholar
  161. 161.
    Jin B, Tao Q, Peng J, Soo HM, Wu W, Ying J, Fields CR, Delmas AL, Liu X, Qiu J, Robertson KD (2008) DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function. Hum Mol Genet 17:690–709PubMedGoogle Scholar
  162. 162.
    Jin F, Dowdy SC, Xiong Y, Eberhardt NL, Podratz KC, Jiang SW (2005) Up-regulation of DNA methyltransferase 3B expression in endometrial cancers. Gynecol Oncol 96:531–538PubMedGoogle Scholar
  163. 163.
    Johnson D, Morrison N, Grant L, Turner T, Fantes J, Connor JM, Murday V (2006) Confirmation of CHD7 as a cause of CHARGE association identified by mapping a balanced chromosome translocation in affected monozygotic twins. J Med Genet 43:280–284PubMedGoogle Scholar
  164. 164.
    Jones JS, Amos CI, Pande M, Gu X, Chen J, Campos IM, Wei Q, Rodriguez-Bigas M, Lynch PM, Frazier ML (2006) DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset. Cancer Epidemiol Biomarkers Prev 15:886–891PubMedGoogle Scholar
  165. 165.
    Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428PubMedGoogle Scholar
  166. 166.
    Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, Wolffe AP (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19:187–191PubMedGoogle Scholar
  167. 167.
    Jones RS (2007) Epigenetics: reversing the ‘irreversible’. Nature 450:357–359PubMedGoogle Scholar
  168. 168.
    Judd BH (1955) Direct proof of a variegated-type position effect at the white locus in Drosophila melanogaster. Genetics 40:739–744PubMedGoogle Scholar
  169. 169.
    Kalkhoven E (2004) CBP and p300: HATs for different occasions. Biochem Pharmacol 68:1145–1155PubMedGoogle Scholar
  170. 170.
    Kalkhoven E, Roelfsema JH, Teunissen H, den Boer A, Ariyurek Y, Zantema A, Breuning MH, Hennekam RC, Peters DJ (2003) Loss of CBP acetyltransferase activity by PHD finger mutations in Rubinstein-Taybi syndrome. Hum Mol Genet 12:441–450PubMedGoogle Scholar
  171. 171.
    Kang S, Elf S, Lythgoe K, Hitosugi T, Taunton J, Zhou W, Xiong L, Wang D, Muller S, Fan S, Sun SY, Marcus AI, Gu TL, Polakiewicz RD, Chen ZG, Khuri FR, Shin DM, Chen J (2010) p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells. J Clin Invest 120:1165–1177PubMedGoogle Scholar
  172. 172.
    Karpf AR, Matsui S (2005) Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells. Cancer Res 65:8635–8639PubMedGoogle Scholar
  173. 173.
    Kernohan KD, Jiang Y, Tremblay DC, Bonvissuto AC, Eubanks JH, Mann MR, Berube NG (2010) ATRX partners with cohesin and MeCP2 and contributes to developmental silencing of imprinted genes in the brain. Dev Cell 18:191–202PubMedGoogle Scholar
  174. 174.
    Kerr SJ (1972) Competing methyltransferase systems. J Biol Chem 247:4248–4252PubMedGoogle Scholar
  175. 175.
    Kim HG, Kurth I, Lan F, Meliciani I, Wenzel W, Eom SH, Kang GB, Rosenberger G, Tekin M, Ozata M, Bick DP, Sherins RJ, Walker SL, Shi Y, Gusella JF, Layman LC (2008) Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet 83:511–519PubMedGoogle Scholar
  176. 176.
    Kim SZ, Santamaria E, Jeong TE, Levy HL, Mato JM, Corrales FJ, Mudd SH (2002) Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation. J Inherit Metab Dis 25:661–671PubMedGoogle Scholar
  177. 177.
    Kimura H, Shiota K (2003) Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1. J Biol Chem 278:4806–4812PubMedGoogle Scholar
  178. 178.
    Klochendler-Yeivin A, Fiette L, Barra J, Muchardt C, Babinet C, Yaniv M (2000) The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression. EMBO Rep 1:500–506PubMedGoogle Scholar
  179. 179.
    Klochendler-Yeivin A, Picarsky E, Yaniv M (2006) Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex. Mol Cell Biol 26:2661–2674PubMedGoogle Scholar
  180. 180.
    Klose RJ, Sarraf SA, Schmiedeberg L, McDermott SM, Stancheva I, Bird AP (2005) DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG. Mol Cell 19:667–678PubMedGoogle Scholar
  181. 181.
    Kohashi K, Oda Y, Yamamoto H, Tamiya S, Oshiro Y, Izumi T, Taguchi T, Tsuneyoshi M (2008) SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma. Am J Surg Pathol 32:1168–1174PubMedGoogle Scholar
  182. 182.
    Kotb M, Mudd SH, Mato JM, Geller AM, Kredich NM, Chou JY, Cantoni GL (1997) Consensus nomenclature for the mammalian methionine adenosyltransferase genes and gene products. Trends Genet 13:51–52PubMedGoogle Scholar
  183. 183.
    Kourmouli N, Sun YM, van der Sar S, Singh PB, Brown JP (2005) Epigenetic regulation of mammalian pericentric heterochromatin in vivo by HP1. Biochem Biophys Res Commun 337:901–907PubMedGoogle Scholar
  184. 184.
    Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705PubMedGoogle Scholar
  185. 185.
    Kreiger PA, Judkins AR, Russo PA, Biegel JA, Lestini BJ, Assanasen C, Pawel BR (2009) Loss of INI1 expression defines a unique subset of pediatric undifferentiated soft tissue sarcomas. Mod Pathol 22:142–150PubMedGoogle Scholar
  186. 186.
    Krueger DD, Bear MF (2011) Toward fulfilling the promise of molecular medicine in fragile X syndrome. Annu Rev Med 62:411–429PubMedGoogle Scholar
  187. 187.
    Kurotaki N, Harada N, Yoshiura K, Sugano S, Niikawa N, Matsumoto N (2001) Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene. Gene 279:197–204PubMedGoogle Scholar
  188. 188.
    Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T, Ohashi H, Naritomi K, Tsukahara M, Makita Y, Sugimoto T, Sonoda T, Hasegawa T, Chinen Y, Tomita Ha HA, Kinoshita A, Mizuguchi T, Yoshiura Ki K, Ohta T, Kishino T, Fukushima Y, Niikawa N, Matsumoto N (2002) Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet 30:365–366PubMedGoogle Scholar
  189. 189.
    Kuwahara Y, Charboneau A, Knudsen ES, Weissman BE (2010) Reexpression of hSNF5 in malignant rhabdoid tumor cell lines causes cell cycle arrest through a p21(CIP1/WAF1)-dependent mechanism. Cancer Res 70:1854–1865PubMedGoogle Scholar
  190. 190.
    Lake RJ, Geyko A, Hemashettar G, Zhao Y, Fan HY (2010) UV-induced association of the CSB remodeling protein with chromatin requires ATP-dependent relief of N-terminal autorepression. Mol Cell 37:235–246PubMedGoogle Scholar
  191. 191.
    Lee S, Cimica V, Ramachandra N, Zagzag D, Kalpana GV (2011) Aurora A is a repressed effector target of the chromatin remodeling protein INI1/hSNF5 required for rhabdoid tumor cell survival. Cancer Res 71:3225–3235PubMedGoogle Scholar
  192. 192.
    Lee SJ, Jeon HS, Jang JS, Park SH, Lee GY, Lee BH, Kim CH, Kang YM, Lee WK, Kam S, Park RW, Kim IS, Cho YL, Jung TH, Park JY (2005) DNMT3B polymorphisms and risk of primary lung cancer. Carcinogenesis 26:403–409PubMedGoogle Scholar
  193. 193.
    Lemmers RJ, van der Vliet PJ, Klooster R, Sacconi S, Camano P, Dauwerse JG, Snider L, Straasheijm KR, van Ommen GJ, Padberg GW, Miller DG, Tapscott SJ, Tawil R, Frants RR, van der Maarel SM (2010) A unifying genetic model for facioscapulohumeral muscular dystrophy. Science 329:1650–1653PubMedGoogle Scholar
  194. 194.
    Lemmers RJ, Wohlgemuth M, van der Gaag KJ, van der Vliet PJ, van Teijlingen CM, de Knijff P, Padberg GW, Frants RR, van der Maarel SM (2007) Specific sequence variations within the 4q35 region are associated with facioscapulohumeral muscular dystrophy. Am J Hum Genet 81:884–894PubMedGoogle Scholar
  195. 195.
    Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jeppesen P, Klein F, Bird A (1992) Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69:905–914PubMedGoogle Scholar
  196. 196.
    Li B, Carey M, Workman JL (2007) The role of chromatin during transcription. Cell 128:707–719PubMedGoogle Scholar
  197. 197.
    Li E (2002) Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet 3:662–673PubMedGoogle Scholar
  198. 198.
    Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926PubMedGoogle Scholar
  199. 199.
    Li J, Ramani K, Sun Z, Zee C, Grant EG, Yang H, Xia M, Oh P, Ko K, Mato JM, Lu SC (2010) Forced expression of methionine adenosyltransferase 1A in human hepatoma cells suppresses in vivo tumorigenicity in mice. Am J Pathol 176:2456–2466PubMedGoogle Scholar
  200. 200.
    Li Y, Dai Y, Wu SL, Pei P, Cao XH, Pu DF (2005) The C46359T polymorphism of DNMT3B promoter gene and pathogenesis of acute leukemia. Zhonghua Nei Ke Za Zhi 44:588–591PubMedGoogle Scholar
  201. 201.
    Li Y, Trojer P, Xu CF, Cheung P, Kuo A, Drury WJ 3rd, Qiao Q, Neubert TA, Xu RM, Gozani O, Reinberg D (2009) The target of the NSD family of histone lysine methyltransferases depends on the nature of the substrate. J Biol Chem 284:34283–34295PubMedGoogle Scholar
  202. 202.
    Liao YJ, Chen KH, Huang SF, Chen TL, Wang CK, Chien CH, Tsai TF, Liu SP, Chen YM (2010) Deficiency of glycine N-methyltransferase results in deterioration of cellular defense to stress in mouse liver. Proteomics Clin Appl 4:394–406PubMedGoogle Scholar
  203. 203.
    Liao YJ, Liu SP, Lee CM, Yen CH, Chuang PC, Chen CY, Tsai TF, Huang SF, Lee YH, Chen YM (2009) Characterization of a glycine N-methyltransferase gene knockout mouse model for hepatocellular carcinoma: implications of the gender disparity in liver cancer susceptibility. Int J Cancer 124:816–826PubMedGoogle Scholar
  204. 204.
    Lin CH, Hsieh SY, Sheen IS, Lee WC, Chen TC, Shyu WC, Liaw YF (2001) Genome-wide hypomethylation in hepatocellular carcinogenesis. Cancer Res 61:4238–4243PubMedGoogle Scholar
  205. 205.
    Lin H, Wong RP, Martinka M, Li G (2009) Loss of SNF5 expression correlates with poor patient survival in melanoma. Clin Cancer Res 15:6404–6411PubMedGoogle Scholar
  206. 206.
    Lin H, Yamada Y, Nguyen S, Linhart H, Jackson-Grusby L, Meissner A, Meletis K, Lo G, Jaenisch R (2006) Suppression of intestinal neoplasia by deletion of Dnmt3b. Mol Cell Biol 26:2976–2983PubMedGoogle Scholar
  207. 207.
    Liu SP, Li YS, Chen YJ, Chiang EP, Li AF, Lee YH, Tsai TF, Hsiao M, Huang SF, Chen YM (2007) Glycine N-methyltransferase-/- mice develop chronic hepatitis and glycogen storage disease in the liver. Hepatology 46:1413–1425PubMedGoogle Scholar
  208. 208.
    Liu Z, Wang L, Wang LE, Sturgis EM, Wei Q (2008) Polymorphisms of the DNMT3B gene and risk of squamous cell carcinoma of the head and neck: a case-control study. Cancer Lett 268:158–165PubMedGoogle Scholar
  209. 209.
    Loenen WA (2006) S-adenosylmethionine: jack of all trades and master of everything? Biochem Soc Trans 34:330–333PubMedGoogle Scholar
  210. 210.
    Lu SC, Alvarez L, Huang ZZ, Chen L, An W, Corrales FJ, Avila MA, Kanel G, Mato JM (2001) Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Proc Natl Acad Sci USA 98:5560–5565PubMedGoogle Scholar
  211. 211.
    Lu T, Jackson MW, Wang B, Yang M, Chance MR, Miyagi M, Gudkov AV, Stark GR (2010) Regulation of NF-kappaB by NSD1/FBXL11-dependent reversible lysine methylation of p65. Proc Natl Acad Sci USA 107:46–51PubMedGoogle Scholar
  212. 212.
    Lucio-Eterovic AK, Singh MM, Gardner JE, Veerappan CS, Rice JC, Carpenter PB (2010) Role for the nuclear receptor-binding SET domain protein 1 (NSD1) methyltransferase in coordinating lysine 36 methylation at histone 3 with RNA polymerase II function. Proc Natl Acad Sci USA 107:16952–16957PubMedGoogle Scholar
  213. 213.
    Luikenhuis S, Giacometti E, Beard CF, Jaenisch R (2004) Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci USA 101:6033–6038PubMedGoogle Scholar
  214. 214.
    Luka Z, Capdevila A, Mato JM, Wagner C (2006) A glycine N-methyltransferase knockout mouse model for humans with deficiency of this enzyme. Transgenic Res 15:393–397PubMedGoogle Scholar
  215. 215.
    Luka Z, Cerone R, Phillips JA 3rd, Mudd HS, Wagner C (2002) Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. Hum Genet 110:68–74PubMedGoogle Scholar
  216. 216.
    Martin-Subero JI, Esteller M (2011) Profiling epigenetic alterations in disease. Adv Exp Med Biol 711:162–177PubMedGoogle Scholar
  217. 217.
    Martinez-Chantar ML, Corrales FJ, Martinez-Cruz LA, Garcia-Trevijano ER, Huang ZZ, Chen L, Kanel G, Avila MA, Mato JM, Lu SC (2002) Spontaneous oxidative stress and liver tumors in mice lacking methionine adenosyltransferase 1A. FASEB J 16:1292–1294PubMedGoogle Scholar
  218. 218.
    Martinez-Chantar ML, Latasa MU, Varela-Rey M, Lu SC, Garcia-Trevijano ER, Mato JM, Avila MA (2003) l-methionine availability regulates expression of the methionine adenosyltransferase 2A gene in human hepatocarcinoma cells: role of S-adenosylmethionine. J Biol Chem 278:19885–19890PubMedGoogle Scholar
  219. 219.
    Martinez-Chantar ML, Vazquez-Chantada M, Ariz U, Martinez N, Varela M, Luka Z, Capdevila A, Rodriguez J, Aransay AM, Matthiesen R, Yang H, Calvisi DF, Esteller M, Fraga M, Lu SC, Wagner C, Mato JM (2008) Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 47:1191–1199PubMedGoogle Scholar
  220. 220.
    Mato JM, Alvarez L, Ortiz P, Pajares MA (1997) S-adenosylmethionine synthesis: molecular mechanisms and clinical implications. Pharmacol Ther 73:265–280PubMedGoogle Scholar
  221. 221.
    Mato JM, Corrales FJ, Lu SC, Avila MA (2002) S-adenosylmethionine: a control switch that regulates liver function. FASEB J 16:15–26PubMedGoogle Scholar
  222. 222.
    Mato JM, Lu SC (2007) Role of S-adenosyl-l-methionine in liver health and injury. Hepatology 45:1306–1312PubMedGoogle Scholar
  223. 223.
    Mayne LV, Lehmann AR (1982) Failure of RNA synthesis to recover after UV irradiation: an early defect in cells from individuals with Cockayne’s syndrome and xeroderma pigmentosum. Cancer Res 42:1473–1478PubMedGoogle Scholar
  224. 224.
    McDowell TL, Gibbons RJ, Sutherland H, O’Rourke DM, Bickmore WA, Pombo A, Turley H, Gatter K, Picketts DJ, Buckle VJ, Chapman L, Rhodes D, Higgs DR (1999) Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes. Proc Natl Acad Sci USA 96:13983–13988PubMedGoogle Scholar
  225. 225.
    McKenna ES, Sansam CG, Cho YJ, Greulich H, Evans JA, Thom CS, Moreau LA, Biegel JA, Pomeroy SL, Roberts CW (2008) Loss of the epigenetic tumor suppressor SNF5 leads to cancer without genomic instability. Mol Cell Biol 28:6223–6233PubMedGoogle Scholar
  226. 226.
    Meda F, Folci M, Baccarelli A, Selmi C (2011) The epigenetics of autoimmunity. Cell Mol Immunol 8:226–236PubMedGoogle Scholar
  227. 227.
    Mehmood T, Schneider A, Sibille J, Marques Pereira P, Pannetier S, Ammar MR, Dembele D, Thibault-Carpentier C, Rouach N, Hanauer A (2011) Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin-Lowry syndrome. Hum Genet 129:255–269PubMedGoogle Scholar
  228. 228.
    Merienne K, Pannetier S, Harel-Bellan A, Sassone-Corsi P (2001) Mitogen-regulated RSK2-CBP interaction controls their kinase and acetylase activities. Mol Cell Biol 21:7089–7096PubMedGoogle Scholar
  229. 229.
    Mila M, Castellvi-Bel S, Sanchez A, Lazaro C, Villa M, Estivill X (1996) Mosaicism for the fragile X syndrome full mutation and deletions within the CGG repeat of the FMR1 gene. J Med Genet 33:338–340PubMedGoogle Scholar
  230. 230.
    Miller RW, Rubinstein JH (1995) Tumors in Rubinstein-Taybi syndrome. Am J Med Genet 56:112–115PubMedGoogle Scholar
  231. 231.
    Miyake K, Hirasawa T, Soutome M, Itoh M, Goto Y, Endoh K, Takahashi K, Kudo S, Nakagawa T, Yokoi S, Taira T, Inazawa J, Kubota T (2011) The protocadherins, PCDHB1 and PCDH7, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome. BMC Neurosci 12:81PubMedGoogle Scholar
  232. 232.
    Moarefi AH, Chedin F (2011) ICF syndrome mutations cause a broad spectrum of biochemical defects in DNMT3B-mediated de novo DNA methylation. J Mol Biol 409:758–772PubMedGoogle Scholar
  233. 233.
    Modena P, Lualdi E, Facchinetti F, Galli L, Teixeira MR, Pilotti S, Sozzi G (2005) SMARCB1/INI1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas. Cancer Res 65:4012–4019PubMedGoogle Scholar
  234. 234.
    Momparler RL, Bovenzi V (2000) DNA methylation and cancer. J Cell Physiol 183:145–154PubMedGoogle Scholar
  235. 235.
    Montgomery KG, Liu MC, Eccles DM, Campbell IG (2004) The DNMT3B C– > T promoter polymorphism and risk of breast cancer in a British population: a case-control study. Breast Cancer Res 6:R390–R394PubMedGoogle Scholar
  236. 236.
    Morgan HD, Sutherland HG, Martin DI, Whitelaw E (1999) Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23:314–318PubMedGoogle Scholar
  237. 237.
    Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA (2011) Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature 476:298–303PubMedGoogle Scholar
  238. 238.
    Mudd SH, Cerone R, Schiaffino MC, Fantasia AR, Minniti G, Caruso U, Lorini R, Watkins D, Matiaszuk N, Rosenblatt DS, Schwahn B, Rozen R, LeGros L, Kotb M, Capdevila A, Luka Z, Finkelstein JD, Tangerman A, Stabler SP, Allen RH, Wagner C (2001) Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia. J Inherit Metab Dis 24:448–464PubMedGoogle Scholar
  239. 239.
    Muers MR, Sharpe JA, Garrick D, Sloane-Stanley J, Nolan PM, Hacker T, Wood WG, Higgs DR, Gibbons RJ (2007) Defining the cause of skewed X-chromosome inactivation in X-linked mental retardation by use of a mouse model. Am J Hum Genet 80:1138–1149PubMedGoogle Scholar
  240. 240.
    Muller H (1930) Types of visible variations induced by X-rays in Drosophila. J Genet 22:299Google Scholar
  241. 241.
    Muotri AR, Marchetto MC, Coufal NG, Oefner R, Yeo G, Nakashima K, Gage FH (2010) L1 retrotransposition in neurons is modulated by MeCP2. Nature 468:443–446PubMedGoogle Scholar
  242. 242.
    Murata T, Kurokawa R, Krones A, Tatsumi K, Ishii M, Taki T, Masuno M, Ohashi H, Yanagisawa M, Rosenfeld MG, Glass CK, Hayashi Y (2001) Defect of histone acetyltransferase activity of the nuclear transcriptional coactivator CBP in Rubinstein-Taybi syndrome. Hum Mol Genet 10:1071–1076PubMedGoogle Scholar
  243. 243.
    Nan X, Hou J, Maclean A, Nasir J, Lafuente MJ, Shu X, Kriaucionis S, Bird A (2007) Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation. Proc Natl Acad Sci USA 104:2709–2714PubMedGoogle Scholar
  244. 244.
    Nan X, Meehan RR, Bird A (1993) Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res 21:4886–4892PubMedGoogle Scholar
  245. 245.
    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 393:386–389PubMedGoogle Scholar
  246. 246.
    Nance MA, Berry SA (1992) Cockayne syndrome: review of 140 cases. Am J Med Genet 42:68–84PubMedGoogle Scholar
  247. 247.
    Newman JC, Bailey AD, Fan HY, Pavelitz T, Weiner AM (2008) An abundant evolutionarily conserved CSB-PiggyBac fusion protein expressed in Cockayne syndrome. PLoS Genet 4:e1000031PubMedGoogle Scholar
  248. 248.
    Newman JC, Bailey AD, Weiner AM (2006) Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling. Proc Natl Acad Sci USA 103:9613–9618PubMedGoogle Scholar
  249. 249.
    Nikitina T, Shi X, Ghosh RP, Horowitz-Scherer RA, Hansen JC, Woodcock CL (2007) Multiple modes of interaction between the methylated DNA binding protein MeCP2 and chromatin. Mol Cell Biol 27:864–877PubMedGoogle Scholar
  250. 250.
    Northcott PA, Nakahara Y, Wu X, Feuk L, Ellison DW, Croul S, Mack S, Kongkham PN, Peacock J, Dubuc A, Ra YS, Zilberberg K, McLeod J, Scherer SW, Sunil Rao J, Eberhart CG, Grajkowska W, Gillespie Y, Lach B, Grundy R, Pollack IF, Hamilton RL, Van Meter T, Carlotti CG, Boop F, Bigner D, Gilbertson RJ, Rutka JT, Taylor MD (2009) Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nat Genet 41:465–472PubMedGoogle Scholar
  251. 251.
    Oelke K, Lu Q, Richardson D, Wu A, Deng C, Hanash S, Richardson B (2004) Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors. Arthritis Rheum 50:1850–1860PubMedGoogle Scholar
  252. 252.
    Ogawa H, Gomi T, Takusagawa F, Fujioka M (1998) Structure, function and physiological role of glycine N-methyltransferase. Int J Biochem Cell Biol 30:13–26PubMedGoogle Scholar
  253. 253.
    Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257PubMedGoogle Scholar
  254. 254.
    Okano M, Xie S, Li E (1998) Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 19:219–220PubMedGoogle Scholar
  255. 255.
    Ostler KR, Davis EM, Payne SL, Gosalia BB, Exposito-Cespedes J, Le Beau MM, Godley LA (2007) Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins. Oncogene 26:5553–5563PubMedGoogle Scholar
  256. 256.
    Ozdag H, Teschendorff AE, Ahmed AA, Hyland SJ, Blenkiron C, Bobrow L, Veerakumarasivam A, Burtt G, Subkhankulova T, Arends MJ, Collins VP, Bowtell D, Kouzarides T, Brenton JD, Caldas C (2006) Differential expression of selected histone modifier genes in human solid cancers. BMC Genomics 7:90PubMedGoogle Scholar
  257. 257.
    Pagon RA, Graham JM Jr, Zonana J, Yong SL (1981) Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. J Pediatr 99:223–227PubMedGoogle Scholar
  258. 258.
    Pallos J, Bodai L, Lukacsovich T, Purcell JM, Steffan JS, Thompson LM, Marsh JL (2008) Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington’s disease. Hum Mol Genet 17:3767–3775PubMedGoogle Scholar
  259. 259.
    Pampal A (2010) CHARGE: an association or a syndrome? Int J Pediatr Otorhinolaryngol 74:719–722PubMedGoogle Scholar
  260. 260.
    Park BL, Kim LH, Shin HD, Park YW, Uhm WS, Bae SC (2004) Association analyses of DNA methyltransferase-1 (DNMT1) polymorphisms with systemic lupus erythematosus. J Hum Genet 49:642–646PubMedGoogle Scholar
  261. 261.
    Park HJ, Yu E, Shim YH (2006) DNA methyltransferase expression and DNA hypermethylation in human hepatocellular carcinoma. Cancer Lett 233:271–278PubMedGoogle Scholar
  262. 262.
    Park YJ, Claus R, Weichenhan D, Plass C (2011) Genome-wide epigenetic modifications in cancer. Prog Drug Res 67:25–49PubMedGoogle Scholar
  263. 263.
    Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC, Boca SM, Carter H, Samayoa J, Bettegowda C, Gallia GL, Jallo GI, Binder ZA, Nikolsky Y, Hartigan J, Smith DR, Gerhard DS, Fults DW, VandenBerg S, Berger MS, Marie SK, Shinjo SM, Clara C, Phillips PC, Minturn JE, Biegel JA, Judkins AR, Resnick AC, Storm PB, Curran T, He Y, Rasheed BA, Friedman HS, Keir ST, McLendon R, Northcott PA, Taylor MD, Burger PC, Riggins GJ, Karchin R, Parmigiani G, Bigner DD, Yan H, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE (2011) The genetic landscape of the childhood cancer medulloblastoma. Science 331:435–439PubMedGoogle Scholar
  264. 264.
    Pauli S, von Velsen N, Burfeind P, Steckel M, Mänz J, Buchholz A, Borozdin W, Kohlhase J (2011) CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin. Clin Genet 81:234PubMedGoogle Scholar
  265. 265.
    Paulson HL, Fischbeck KH (1996) Trinucleotide repeats in neurogenetic disorders. Annu Rev Neurosci 19:79–107PubMedGoogle Scholar
  266. 266.
    Petri M (2002) Epidemiology of systemic lupus erythematosus. Best Pract Res Clin Rheumatol 16:847–858PubMedGoogle Scholar
  267. 267.
    Petrij F, Dauwerse HG, Blough RI, Giles RH, van der Smagt JJ, Wallerstein R, Maaswinkel-Mooy PD, van Karnebeek CD, van Ommen GJ, van Haeringen A, Rubinstein JH, Saal HM, Hennekam RC, Peters DJ, Breuning MH (2000) Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations. J Med Genet 37:168–176PubMedGoogle Scholar
  268. 268.
    Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, Masuno M, Tommerup N, van Ommen GJ, Goodman RH, Peters DJ et al (1995) Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376:348–351PubMedGoogle Scholar
  269. 269.
    Petronis A (2010) Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature 465:721–727PubMedGoogle Scholar
  270. 270.
    Petrov A, Pirozhkova I, Carnac G, Laoudj D, Lipinski M, Vassetzky YS (2006) Chromatin loop domain organization within the 4q35 locus in facioscapulohumeral dystrophy patients versus normal human myoblasts. Proc Natl Acad Sci USA 103:6982–6987PubMedGoogle Scholar
  271. 271.
    Pradhan S, Bacolla A, Wells RD, Roberts RJ (1999) Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem 274:33002–33010PubMedGoogle Scholar
  272. 272.
    Rajender S, Avery K, Agarwal A (2011) Epigenetics, spermatogenesis and male infertility. Mutat Res 727:62–71PubMedGoogle Scholar
  273. 273.
    Rakyan VK, Blewitt ME, Druker R, Preis JI, Whitelaw E (2002) Metastable epialleles in mammals. Trends Genet 18:348–351PubMedGoogle Scholar
  274. 274.
    Rakyan VK, Chong S, Champ ME, Cuthbert PC, Morgan HD, Luu KV, Whitelaw E (2003) Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci USA 100:2538–2543PubMedGoogle Scholar
  275. 275.
    Ramocki MB, Tavyev YJ, Peters SU (2010) The MECP2 duplication syndrome. Am J Med Genet A 152A:1079–1088PubMedGoogle Scholar
  276. 276.
    Rapin I, Lindenbaum Y, Dickson DW, Kraemer KH, Robbins JH (2000) Cockayne syndrome and xeroderma pigmentosum. Neurology 55:1442–1449PubMedGoogle Scholar
  277. 277.
    Rayasam GV, Wendling O, Angrand PO, Mark M, Niederreither K, Song L, Lerouge T, Hager GL, Chambon P, Losson R (2003) NSD1 is essential for early post-implantation development and has a catalytically active SET domain. EMBO J 22:3153–3163PubMedGoogle Scholar
  278. 278.
    Reed SC (1937) The Inheritance and Expression of Fused, a New Mutation in the House Mouse. Genetics 22:1–13PubMedGoogle Scholar
  279. 279.
    Reik W (1988) Genomic imprinting: a possible mechanism for the parental origin effect in Huntington’s chorea. J Med Genet 25:805–808PubMedGoogle Scholar
  280. 280.
    Richardson B (1986) Effect of an inhibitor of DNA methylation on T cells. II. 5-Azacytidine induces self-reactivity in antigen-specific T4+ cells. Hum Immunol 17:456–470PubMedGoogle Scholar
  281. 281.
    Richardson B, Powers D, Hooper F, Yung RL, O’Rourke K (1994) Lymphocyte function-associated antigen 1 overexpression and T cell autoreactivity. Arthritis Rheum 37:1363–1372PubMedGoogle Scholar
  282. 282.
    Richardson BC, Strahler JR, Pivirotto TS, Quddus J, Bayliss GE, Gross LA, O’Rourke KS, Powers D, Hanash SM, Johnson MA (1992) Phenotypic and functional similarities between 5-azacytidine-treated T cells and a T cell subset in patients with active systemic lupus erythematosus. Arthritis Rheum 35:647–662PubMedGoogle Scholar
  283. 283.
    Ridley RM, Frith CD, Crow TJ, Conneally PM (1988) Anticipation in Huntington’s disease is inherited through the male line but may originate in the female. J Med Genet 25:589–595PubMedGoogle Scholar
  284. 284.
    Roberts CW, Galusha SA, McMenamin ME, Fletcher CD, Orkin SH (2000) Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice. Proc Natl Acad Sci USA 97:13796–13800PubMedGoogle Scholar
  285. 285.
    Robertson KD (2001) DNA methylation, methyltransferases, and cancer. Oncogene 20:3139–3155PubMedGoogle Scholar
  286. 286.
    Robertson KD (2005) DNA methylation and human disease. Nat Rev Genet 6:597–610PubMedGoogle Scholar
  287. 287.
    Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA (1999) The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res 27:2291–2298PubMedGoogle Scholar
  288. 288.
    Roelfsema JH, Peters DJ (2007) Rubinstein-Taybi syndrome: clinical and molecular overview. Expert Rev Mol Med 9:1–16PubMedGoogle Scholar
  289. 289.
    Roelfsema JH, White SJ, Ariyurek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, den Dunnen JT, van Ommen GJ, Breuning MH, Hennekam RC, Peters DJ (2005) Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet 76:572–580PubMedGoogle Scholar
  290. 290.
    Rubinstein JH, Taybi H (1963) Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome. Am J Dis Child 105:588–608PubMedGoogle Scholar
  291. 291.
    Rubinsztein DC, Leggo J, Coles R, Almqvist E, Biancalana V, Cassiman JJ, Chotai K, Connarty M, Crauford D, Curtis A, Curtis D, Davidson MJ, Differ AM, Dode C, Dodge A, Frontali M, Ranen NG, Stine OC, Sherr M, Abbott MH, Franz ML, Graham CA, Harper PS, Hedreen JC, Hayden MR et al (1996) Phenotypic characterization of individuals with 30–40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36–39 repeats. Am J Hum Genet 59:16–22PubMedGoogle Scholar
  292. 292.
    Ryu H, Lee J, Hagerty SW, Soh BY, McAlpin SE, Cormier KA, Smith KM, Ferrante RJ (2006) ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington’s disease. Proc Natl Acad Sci USA 103:19176–19181PubMedGoogle Scholar
  293. 293.
    Sabl JF, Laird CD (1992) Epigene conversion: a proposal with implications for gene mapping in humans. Am J Hum Genet 50:1171–1177PubMedGoogle Scholar
  294. 294.
    Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S (2002) Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis. Proc Natl Acad Sci USA 99:10060–10065PubMedGoogle Scholar
  295. 295.
    Sanka M, Tangsinmankong N, Loscalzo M, Sleasman JW, Dorsey MJ (2007) Complete DiGeorge syndrome associated with CHD7 mutation. J Allergy Clin Immunol 120:952–954PubMedGoogle Scholar
  296. 296.
    Sasai N, Defossez PA (2009) Many paths to one goal? The proteins that recognize methylated DNA in eukaryotes. Int J Dev Biol 53:323–334PubMedGoogle Scholar
  297. 297.
    Satyal SH, Schmidt E, Kitagawa K, Sondheimer N, Lindquist S, Kramer JM, Morimoto RI (2000) Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc Natl Acad Sci USA 97:5750–5755PubMedGoogle Scholar
  298. 298.
    Sawalha AH, Richardson B (2005) DNA Methylation in the Pathogenesis of Systemic Lupus Erythematosus Current Pharmacogenomics 3:73–78Google Scholar
  299. 299.
    Sawalha AH, Webb R, Han S, Kelly JA, Kaufman KM, Kimberly RP, Alarcon-Riquelme ME, James JA, Vyse TJ, Gilkeson GS, Choi CB, Scofield RH, Bae SC, Nath SK, Harley JB (2008) Common variants within MECP2 confer risk of systemic lupus erythematosus. PLoS One 3:e1727PubMedGoogle Scholar
  300. 300.
    Scarpa P, Faggioli R, Voghenzi A (1994) Familial Sotos syndrome: longitudinal study of two additional cases. Genet Couns 5:155–159PubMedGoogle Scholar
  301. 301.
    Schmickel RD, Chu EH, Trosko JE, Chang CC (1977) Cockayne syndrome: a cellular sensitivity to ultraviolet light. Pediatrics 60:135–139PubMedGoogle Scholar
  302. 302.
    Schmid M, Haaf T, Grunert D (1984) 5-Azacytidine-induced undercondensations in human chromosomes. Hum Genet 67:257–263PubMedGoogle Scholar
  303. 303.
    Schmidt WM, Sedivy R, Forstner B, Steger GG, Zochbauer-Muller S, Mader RM (2007) Progressive up-regulation of genes encoding DNA methyltransferases in the colorectal adenoma-carcinoma sequence. Mol Carcinog 46:766–772PubMedGoogle Scholar
  304. 304.
    Schnetz MP, Bartels CF, Shastri K, Balasubramanian D, Zentner GE, Balaji R, Zhang X, Song L, Wang Z, Laframboise T, Crawford GE, Scacheri PC (2009) Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. Genome Res 19:590–601PubMedGoogle Scholar
  305. 305.
    Scofield RH, Bruner GR, Namjou B, Kimberly RP, Ramsey-Goldman R, Petri M, Reveille JD, Alarcon GS, Vila LM, Reid J, Harris B, Li S, Kelly JA, Harley JB (2008) Klinefelter’s syndrome (47, XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum 58:2511–2517PubMedGoogle Scholar
  306. 306.
    Shen H, Wang L, Spitz MR, Hong WK, Mao L, Wei Q (2002) A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer. Cancer Res 62:4992–4995PubMedGoogle Scholar
  307. 307.
    Shibayama A, Cook EH Jr, Feng J, Glanzmann C, Yan J, Craddock N, Jones IR, Goldman D, Heston LL, Sommer SS (2004) MECP2 structural and 3′-UTR variants in schizophrenia, autism and other psychiatric diseases: a possible association with autism. Am J Med Genet B Neuropsychiatr Genet 128B:50–53PubMedGoogle Scholar
  308. 308.
    Simon JA, Kingston RE (2009) Mechanisms of Polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol 10:697–708PubMedGoogle Scholar
  309. 309.
    Singal R, Das PM, Manoharan M, Reis IM, Schlesselman JJ (2005) Polymorphisms in the DNA methyltransferase 3b gene and prostate cancer risk. Oncol Rep 14:569–573PubMedGoogle Scholar
  310. 310.
    Smeets DF, Moog U, Weemaes CM, Vaes-Peeters G, Merkx GF, Niehof JP, Hamers G (1994) ICF syndrome: a new case and review of the literature. Hum Genet 94:240–246PubMedGoogle Scholar
  311. 311.
    Smith A, Farrar JR, Silink M, Judzewitsch R (1981) Investigations in dominant Sotos syndrome. Ann Genet 24:226–228PubMedGoogle Scholar
  312. 312.
    Smith CL, Peterson CL (2005) ATP-dependent chromatin remodeling. Curr Top Dev Biol 65:115–148PubMedGoogle Scholar
  313. 313.
    Snider L, Geng LN, Lemmers RJ, Kyba M, Ware CB, Nelson AM, Tawil R, Filippova GN, van der Maarel SM, Tapscott SJ, Miller DG (2010) Facioscapulohumeral dystrophy: incomplete suppression of a retrotransposed gene. PLoS Genet 6:e1001181PubMedGoogle Scholar
  314. 314.
    Song J, Rechkoblit O, Bestor TH, Patel DJ (2011) Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science 331:1036–1040PubMedGoogle Scholar
  315. 315.
    Sotos JF, Dodge PR, Muirhead D, Crawford JD, Talbot NB (1964) Cerebral Gigantism in Childhood. A Syndrome of Excessively Rapid Growth and Acromegalic Features and a Nonprogressive Neurologic Disorder. N Engl J Med 271:109–116PubMedGoogle Scholar
  316. 316.
    Srivastava K, Srivastava A, Mittal B (2010) DNMT3B -579 G > T promoter polymorphism and risk of gallbladder carcinoma in North Indian population. J Gastrointest Cancer 41:248–253PubMedGoogle Scholar
  317. 317.
    Statland JM, Tawil R (2011) Facioscapulohumeral muscular dystrophy: molecular pathological advances and future directions. Curr Opin Neurol 24:423–428PubMedGoogle Scholar
  318. 318.
    Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, Apostol BL, Kazantsev A, Schmidt E, Zhu YZ, Greenwald M, Kurokawa R, Housman DE, Jackson GR, Marsh JL, Thompson LM (2001) Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413:739–743PubMedGoogle Scholar
  319. 319.
    Stevenson RE, Abidi F, Schwartz CE, Lubs HA, Holmes LB (2000) Holmes-Gang syndrome is allelic with XLMR-hypotonic face syndrome. Am J Med Genet 94:383–385PubMedGoogle Scholar
  320. 320.
    Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S (2004) DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J Biol Chem 279:27816–27823PubMedGoogle Scholar
  321. 321.
    Sun CY, van Koningsbruggen S, Long SW, Straasheijm K, Klooster R, Jones TI, Bellini M, Levesque L, Brieher WM, van der Maarel SM, Jones PL (2011) Facioscapulohumeral muscular dystrophy region gene 1 is a dynamic RNA-associated and actin-bundling protein. J Mol Biol 411:397–416PubMedGoogle Scholar
  322. 322.
    Takata Y, Huang Y, Komoto J, Yamada T, Konishi K, Ogawa H, Gomi T, Fujioka M, Takusagawa F (2003) Catalytic mechanism of glycine N-methyltransferase. Biochemistry 42:8394–8402PubMedGoogle Scholar
  323. 323.
    Tang P, Frankenberg S, Argentaro A, Graves JM, Familari M (2011) Comparative analysis of the ATRX promoter and 5′ regulatory region reveals conserved regulatory elements which are linked to roles in neurodevelopment, alpha-globin regulation and testicular function. BMC Res Notes 4:200PubMedGoogle Scholar
  324. 324.
    Tatton-Brown K, Rahman N (2007) Sotos syndrome. Eur J Hum Genet 15:264–271PubMedGoogle Scholar
  325. 325.
    Tawil R, Figlewicz DA, Griggs RC, Weiffenbach B (1998) Facioscapulohumeral dystrophy: a distinct regional myopathy with a novel molecular pathogenesis. FSH Consortium. Ann Neurol 43:279–282Google Scholar
  326. 326.
    Tawil R, Van Der Maarel SM (2006) Facioscapulohumeral muscular dystrophy. Muscle Nerve 34:1–15PubMedGoogle Scholar
  327. 327.
    Taylor MD, Gokgoz N, Andrulis IL, Mainprize TG, Drake JM, Rutka JT (2000) Familial posterior fossa brain tumors of infancy secondary to germline mutation of the hSNF5 gene. Am J Hum Genet 66:1403–1406PubMedGoogle Scholar
  328. 328.
    Telenius H, Kremer HP, Theilmann J, Andrew SE, Almqvist E, Anvret M, Greenberg C, Greenberg J, Lucotte G, Squitieri F et al (1993) Molecular analysis of juvenile Huntington disease: the major influence on (CAG)n repeat length is the sex of the affected parent. Hum Mol Genet 2:1535–1540PubMedGoogle Scholar
  329. 329.
    Thienpont B, de Ravel T, Van Esch H, Van Schoubroeck D, Moerman P, Vermeesch JR, Fryns JP, Froyen G, Lacoste C, Badens C, Devriendt K (2007) Partial duplications of the ATRX gene cause the ATR-X syndrome. Eur J Hum Genet 15:1094–1097PubMedGoogle Scholar
  330. 330.
    Thomas EA, Coppola G, Desplats PA, Tang B, Soragni E, Burnett R, Gao F, Fitzgerald KM, Borok JF, Herman D, Geschwind DH, Gottesfeld JM (2008) The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington’s disease transgenic mice. Proc Natl Acad Sci USA 105:15564–15569PubMedGoogle Scholar
  331. 331.
    Tiepolo (1979) Multibranched chromosomes 1, 9, and 16 in a patient with combined IgA and IgE deficiency. Hum Genet 51:127–137PubMedGoogle Scholar
  332. 332.
    Trivier E, De Cesare D, Jacquot S, Pannetier S, Zackai E, Young I, Mandel JL, Sassone-Corsi P, Hanauer A (1996) Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. Nature 384:567–570PubMedGoogle Scholar
  333. 333.
    Tseng TL, Shih YP, Huang YC, Wang CK, Chen PH, Chang JG, Yeh KT, Chen YM, Buetow KH (2003) Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer. Cancer Res 63:647–654PubMedGoogle Scholar
  334. 334.
    Tuck-Muller CM, Narayan A, Tsien F, Smeets DF, Sawyer J, Fiala ES, Sohn OS, Ehrlich M (2000) DNA hypomethylation and unusual chromosome instability in cell lines from ICF syndrome patients. Cytogenet Cell Genet 89:121–128PubMedGoogle Scholar
  335. 335.
    Tupler R, Berardinelli A, Barbierato L, Frants R, Hewitt JE, Lanzi G, Maraschio P, Tiepolo L (1996) Monosomy of distal 4q does not cause facioscapulohumeral muscular dystrophy. J Med Genet 33:366–370PubMedGoogle Scholar
  336. 336.
    Turner BM (2002) Cellular memory and the histone code. Cell 111:285–291PubMedGoogle Scholar
  337. 337.
    Ueda Y, Okano M, Williams C, Chen T, Georgopoulos K, Li E (2006) Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome. Development 133:1183–1192PubMedGoogle Scholar
  338. 338.
    Urdinguio RG, Sanchez-Mut JV, Esteller M (2009) Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol 8:1056–1072PubMedGoogle Scholar
  339. 339.
    van Deutekom JC, Wijmenga C, van Tienhoven EA, Gruter AM, Hewitt JE, Padberg GW, van Ommen GJ, Hofker MH, Frants RR (1993) FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum Mol Genet 2:2037–2042PubMedGoogle Scholar
  340. 340.
    van Overveld PG, Enthoven L, Ricci E, Rossi M, Felicetti L, Jeanpierre M, Winokur ST, Frants RR, Padberg GW, van der Maarel SM (2005) Variable hypomethylation of D4Z4 in facioscapulohumeral muscular dystrophy. Ann Neurol 58:569–576PubMedGoogle Scholar
  341. 341.
    Varela-Rey M, Fernandez-Ramos D, Martinez-Lopez N, Embade N, Gomez-Santos L, Beraza N, Vazquez-Chantada M, Rodriguez J, Luka Z, Wagner C, Lu SC, Martinez-Chantar ML, Mato JM (2009) Impaired liver regeneration in mice lacking glycine N-methyltransferase. Hepatology 50:443–452PubMedGoogle Scholar
  342. 342.
    Varela-Rey M, Martinez-Lopez N, Fernandez-Ramos D, Embade N, Calvisi DF, Woodhoo A, Rodriguez J, Fraga MF, Julve J, Rodriguez-Millan E, Frades I, Torres L, Luka Z, Wagner C, Esteller M, Lu SC, Martinez-Chantar ML, Mato JM (2010) Fatty liver and fibrosis in glycine N-methyltransferase knockout mice is prevented by nicotinamide. Hepatology 52:105–114PubMedGoogle Scholar
  343. 343.
    Vasicek TJ, Zeng L, Guan XJ, Zhang T, Costantini F, Tilghman SM (1997) Two dominant mutations in the mouse fused gene are the result of transposon insertions. Genetics 147:777–786PubMedGoogle Scholar
  344. 344.
    Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, Aurias A, Delattre O (1998) Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394:203–206PubMedGoogle Scholar
  345. 345.
    Viegas-Pequignot E, Dutrillaux B (1976) Segmentation of human chromosomes induced by 5-ACR (5-azacytidine). Hum Genet 34:247–254PubMedGoogle Scholar
  346. 346.
    Vilkaitis G, Suetake I, Klimasauskas S, Tajima S (2005) Processive methylation of hemimethylated CpG sites by mouse Dnmt1 DNA methyltransferase. J Biol Chem 280:64–72PubMedGoogle Scholar
  347. 347.
    Villard L, Fontes M, Ades LC, Gecz J (2000) Identification of a mutation in the XNP/ATR-X gene in a family reported as Smith-Fineman-Myers syndrome. Am J Med Genet 91:83–85PubMedGoogle Scholar
  348. 348.
    Villard L, Gecz J, Mattei JF, Fontes M, Saugier-Veber P, Munnich A, Lyonnet S (1996) XNP mutation in a large family with Juberg-Marsidi syndrome. Nat Genet 12:359–360PubMedGoogle Scholar
  349. 349.
    Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB, Janssen IM, van der Vliet WA, Huys EH, de Jong PJ, Hamel BC, Schoenmakers EF, Brunner HG, Veltman JA, van Kessel AG (2004) Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet 36:955–957PubMedGoogle Scholar
  350. 350.
    Vonsattel JP, DiFiglia M (1998) Huntington disease. J Neuropathol Exp Neurol 57:369–384PubMedGoogle Scholar
  351. 351.
    Wagner C, Briggs WT, Cook RJ (1985) Inhibition of glycine N-methyltransferase activity by folate derivatives: implications for regulation of methyl group metabolism. Biochem Biophys Res Commun 127:746–752PubMedGoogle Scholar
  352. 352.
    Wakeland EK, Liu K, Graham RR, Behrens TW (2001) Delineating the genetic basis of systemic lupus erythematosus. Immunity 15:397–408PubMedGoogle Scholar
  353. 353.
    Wallace LM, Garwick-Coppens SE, Tupler R, Harper SQ (2011) RNA Interference improves myopathic phenotypes in mice over-expressing FSHD region gene 1 (FRG1). Mol Ther 19:2048PubMedGoogle Scholar
  354. 354.
    Wang J, Walsh G, Liu DD, Lee JJ, Mao L (2006) Expression of Delta DNMT3B variants and its association with promoter methylation of p16 and RASSF1A in primary non-small cell lung cancer. Cancer Res 66:8361–8366PubMedGoogle Scholar
  355. 355.
    Wang L, Rodriguez M, Kim ES, Xu Y, Bekele N, El-Naggar AK, Hong WK, Mao L, Oh YW (2004) A novel C/T polymorphism in the core promoter of human de novo cytosine DNA methyltransferase 3B6 is associated with prognosis in head and neck cancer. Int J Oncol 25:993–999PubMedGoogle Scholar
  356. 356.
    Wang L, Wang J, Sun S, Rodriguez M, Yue P, Jang SJ, Mao L (2006) A novel DNMT3B subfamily, DeltaDNMT3B, is the predominant form of DNMT3B in non-small cell lung cancer. Int J Oncol 29:201–207PubMedGoogle Scholar
  357. 357.
    Wang W, Cote J, Xue Y, Zhou S, Khavari PA, Biggar SR, Muchardt C, Kalpana GV, Goff SP, Yaniv M, Workman JL, Crabtree GR (1996) Purification and biochemical heterogeneity of the mammalian SWI-SNF complex. EMBO J 15:5370–5382PubMedGoogle Scholar
  358. 358.
    Wang YM, Wang R, Wen DG, Li Y, Guo W, Wang N, Wei LZ, He YT, Chen ZF, Zhang XF, Zhang JH (2005) Single-nucleotide polymorphism in DNA methyltransferase 3B promoter and its association with gastric cardiac adenocarcinoma in North China. World J Gastroenterol 11:3623–3627PubMedGoogle Scholar
  359. 359.
    Waterland RA, Dolinoy DC, Lin JR, Smith CA, Shi X, Tahiliani KG (2006) Maternal methyl supplements increase offspring DNA methylation at Axin Fused. Genesis 44:401–406PubMedGoogle Scholar
  360. 360.
    Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854PubMedGoogle Scholar
  361. 361.
    Whitelaw NC, Whitelaw E (2008) Transgenerational epigenetic inheritance in health and disease. Curr Opin Genet Dev 18:273–279PubMedGoogle Scholar
  362. 362.
    Wijmenga C, Hansen RS, Gimelli G, Bjorck EJ, Davies EG, Valentine D, Belohradsky BH, van Dongen JJ, Smeets DF, van den Heuvel LP, Luyten JA, Strengman E, Weemaes C, Pearson PL (2000) Genetic variation in ICF syndrome: evidence for genetic heterogeneity. Hum Mutat 16:509–517PubMedGoogle Scholar
  363. 363.
    Winship IM (1985) Sotos syndrome–autosomal dominant inheritance substantiated. Clin Genet 28:243–246PubMedGoogle Scholar
  364. 364.
    Wu Y, Lin JS (2007) DNA methyltransferase 3B promoter polymorphism and its susceptibility to primary hepatocellular carcinoma in the Chinese Han nationality population: a case-control study. World J Gastroenterol 13:6082–6086PubMedGoogle Scholar
  365. 365.
    Xie ZH, Huang YN, Chen ZX, Riggs AD, Ding JP, Gowher H, Jeltsch A, Sasaki H, Hata K, Xu GL (2006) Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L. Hum Mol Genet 15:1375–1385PubMedGoogle Scholar
  366. 366.
    Xu GL, Bestor TH, Bourc’his D, Hsieh CL, Tommerup N, Bugge M, Hulten M, Qu X, Russo JJ, Viegas-Pequignot E (1999) Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402:187–191PubMedGoogle Scholar
  367. 367.
    Xue Y, Gibbons R, Yan Z, Yang D, McDowell TL, Sechi S, Qin J, Zhou S, Higgs D, Wang W (2003) The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies. Proc Natl Acad Sci USA 100:10635–10640PubMedGoogle Scholar
  368. 368.
    Yanagisawa Y, Ito E, Yuasa Y, Maruyama K (2002) The human DNA methyltransferases DNMT3A and DNMT3B have two types of promoters with different CpG contents. Biochim Biophys Acta 1577:457–465PubMedGoogle Scholar
  369. 369.
    Yang H, Huang ZZ, Zeng Z, Chen C, Selby RR, Lu SC (2001) Role of promoter methylation in increased methionine adenosyltransferase 2A expression in human liver cancer. Am J Physiol Gastrointest Liver Physiol 280:G184–G190PubMedGoogle Scholar
  370. 370.
    Yao TP, Oh SP, Fuchs M, Zhou ND, Ch’ng LE, Newsome D, Bronson RT, Li E, Livingston DM, Eckner R (1998) Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93:361–372PubMedGoogle Scholar
  371. 371.
    Ye C, Beeghly-Fadiel A, Lu W, Long J, Shu XO, Gao YT, Zheng W, Cai Q (2010) Two-stage case-control study of DNMT-1 and DNMT-3B gene variants and breast cancer risk. Breast Cancer Res Treat 121:765–769PubMedGoogle Scholar
  372. 372.
    Yen TT, Gill AM, Frigeri LG, Barsh GS, Wolff GL (1994) Obesity, diabetes, and neoplasia in yellow A(vy)/- mice: ectopic expression of the agouti gene. FASEB J 8:479–488PubMedGoogle Scholar
  373. 373.
    Yeo EJ, Wagner C (1994) Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver. Proc Natl Acad Sci USA 91:210–214PubMedGoogle Scholar
  374. 374.
    Yoon JH, Smith LE, Feng Z, Tang M, Lee CS, Pfeifer GP (2001) Methylated CpG dinucleotides are the preferential targets for G-to-T transversion mutations induced by benzo[a]pyrene diol epoxide in mammalian cells: similarities with the p53 mutation spectrum in smoking-associated lung cancers. Cancer Res 61:7110–7117PubMedGoogle Scholar
  375. 375.
    Young JI, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB, Rose MF, Kang D, Richman R, Johnson JM, Berget S, Zoghbi HY (2005) Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc Natl Acad Sci USA 102:17551–17558PubMedGoogle Scholar
  376. 376.
    Yung RL, Quddus J, Chrisp CE, Johnson KJ, Richardson BC (1995) Mechanism of drug-induced lupus. I. Cloned Th2 cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. J Immunol 154:3025–3035PubMedGoogle Scholar
  377. 377.
    Yung RL, Richardson BC (1994) Drug-induced lupus. Rheum Dis Clin North Am 20:61–86PubMedGoogle Scholar
  378. 378.
    Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL 3rd, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F (1997) The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell 90:181–192PubMedGoogle Scholar
  379. 379.
    Zeng W, de Greef JC, Chen YY, Chien R, Kong X, Gregson HC, Winokur ST, Pyle A, Robertson KD, Schmiesing JA, Kimonis VE, Balog J, Frants RR, Ball AR Jr, Lock LF, Donovan PJ, van der Maarel SM, Yokomori K (2009) Specific loss of histone H3 lysine 9 trimethylation and HP1gamma/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD). PLoS Genet 5:e1000559PubMedGoogle Scholar
  380. 380.
    Zeniou-Meyer M, Begle A, Bader MF, Vitale N (2009) The Coffin-Lowry syndrome-associated protein RSK2 controls neuroendocrine secretion through the regulation of phospholipase D1 at the exocytotic sites. Ann N Y Acad Sci 1152:201–208PubMedGoogle Scholar
  381. 381.
    Zentner GE, Hurd EA, Schnetz MP, Handoko L, Wang C, Wang Z, Wei C, Tesar PJ, Hatzoglou M, Martin DM, Scacheri PC (2010) CHD7 functions in the nucleolus as a positive regulator of ribosomal RNA biogenesis. Hum Mol Genet 19:3491–3501PubMedGoogle Scholar
  382. 382.
    Zentner GE, Layman WS, Martin DM, Scacheri PC (2010) Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome. Am J Med Genet A 152A:674–686PubMedGoogle Scholar
  383. 383.
    Zhao M, Wu X, Zhang Q, Luo S, Liang G, Su Y, Tan Y, Lu Q (2010) RFX1 regulates CD70 and CD11a expression in lupus T cells by recruiting the histone methyltransferase SUV39H1. Arthritis Res Ther 12:R227PubMedGoogle Scholar
  384. 384.
    Zimmermann N, Acosta AM, Kohlhase J, Bartsch O (2007) Confirmation of EP300 gene mutations as a rare cause of Rubinstein-Taybi syndrome. Eur J Hum Genet 15:837–842PubMedGoogle Scholar
  385. 385.
    Zonana J, Sotos JF, Romshe CA, Fisher DA, Elders MJ, Rimoin DL (1977) Dominant inheritance of cerebral gigantism. J Pediatr 91:251–256PubMedGoogle Scholar
  386. 386.
    Zraly CB, Dingwall AK (2012) The chromatin remodeling and mRNA splicing functions of the Brahma (SWI/SNF) complex are mediated by the SNR1/SNF5 regulatory subunit. Nucleic Acids Res 40:5975–5987PubMedGoogle Scholar

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Covadonga Huidobro
    • 1
  • Agustin F. Fernandez
    • 1
  • Mario F. Fraga
    • 1
    • 2
    Email author
  1. 1.Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA-HUCA)University of OviedoOviedoSpain
  2. 2.Department of Immunology and OncologyCentro Nacional de Biotecnología (CNB-CSIC)MadridSpain

Personalised recommendations