Human Genetics

, Volume 132, Issue 4, pp 359–383 | Cite as

Genetic syndromes caused by mutations in epigenetic genes

Review Paper

Abstract

The orchestrated organization of epigenetic factors that control chromatin dynamism, including DNA methylation, histone marks, non-coding RNAs (ncRNAs) and chromatin-remodeling proteins, is essential for the proper function of tissue homeostasis, cell identity and development. Indeed, deregulation of epigenetic profiles has been described in several human pathologies, including complex diseases (such as cancer, cardiovascular and neurological diseases), metabolic pathologies (type 2 diabetes and obesity) and imprinting disorders. Over the last decade it has become increasingly clear that mutations of genes involved in epigenetic mechanism, such as DNA methyltransferases, methyl-binding domain proteins, histone deacetylases, histone methylases and members of the SWI/SNF family of chromatin remodelers are linked to human disorders, including Immunodeficiency Centromeric instability Facial syndrome 1, Rett syndrome, Rubinstein–Taybi syndrome, Sotos syndrome or alpha-thalassemia/mental retardation X-linked syndrome, among others. As new members of the epigenetic machinery are described, the number of human syndromes associated with epigenetic alterations increases. As recent examples, mutations of histone demethylases and members of the non-coding RNA machinery have recently been associated with Kabuki syndrome, Claes-Jensen X-linked mental retardation syndrome and Goiter syndrome. In this review, we describe the variety of germline mutations of epigenetic modifiers that are known to be associated with human disorders, and discuss the therapeutic potential of epigenetic drugs as palliative care strategies in the treatment of such disorders.

References

  1. Aapola U, Liiv I, Peterson P (2002) Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity. Nucleic Acids Res 30(16):3602–3608PubMedCrossRefGoogle Scholar
  2. 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-prime alternatively spliced region of the XNP/ATR-X gene causes Chudley-Lowry syndrome. Europ J Hum Genet 13:176–183PubMedCrossRefGoogle Scholar
  3. Abidi FE, Miano MG, Murray JC, Schwartz CE (2007) A novel mutation in the PHF8 gene is associated with X-linked mental retardation with cleft lip/cleft palate. Clin Genet 72:19–22PubMedCrossRefGoogle Scholar
  4. Abidi FE, Holloway L, Moore CA, Weaver DD, Simensen RJ, Stevenson RE, Rogers RC, Schwartz CE (2008) Mutations in JARID1C are associated with X-linked mental retardation, short stature and hyperreflexia. J Med Genet 45:787–793PubMedCrossRefGoogle Scholar
  5. Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP ± mice: a model for the cognitive defect in Rubinstein-Taybi syndrome and its amelioration. Neuron 42:947–959PubMedCrossRefGoogle Scholar
  6. Aldred MA, Sanford ROC, Thomas NS, Barrow MA, Wilson LC, Brueton LA, Bonaglia MC, Hennekam RCM, Eng C, Dennis NR, Trembath RC (2004) Molecular analysis of 20 patients with 2q37.3 monosomy: definition of minimum deletion intervals for key phenotypes. J Med Genet 41:433–439PubMedCrossRefGoogle Scholar
  7. 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(2):185–188PubMedCrossRefGoogle Scholar
  8. Anindya R, Mari PO, Kristensen U, Kool H, Giglia-Mari G, Mullenders LH, Fousteri M, Vermeulen W, Egly JM, Svejstrup JQ (2010) A ubiquitin-binding domain in Cockayne syndrome B required for transcription-coupled nucleotide excision repair. Mol Cell 38(5):637–648PubMedCrossRefGoogle Scholar
  9. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351(3):602–611PubMedCrossRefGoogle Scholar
  10. Arany Z, Sellers WR, Livingston DM, Eckner R (1994) E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators. Cell 77(6):799–800PubMedCrossRefGoogle Scholar
  11. 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(29):11939–11944PubMedCrossRefGoogle Scholar
  12. Arnold MA, Kim Y, Czubryt MP, Phan D, McAnally J, Qi X, Shelton JM, Richardson JA, Bassel-Duby R, Olson EN (2007) MEF2C transcription factor controls chondrocyte hypertrophy and bone development. Dev Cell 12(3):377–389PubMedCrossRefGoogle Scholar
  13. Aziz A, Liu QC, Dilworth FJ (2010) Regulating a master regulator: establishing tissue-specific gene expression in skeletal muscle. Epigenetics 5(8):691–695PubMedCrossRefGoogle Scholar
  14. 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(7283):958–962PubMedCrossRefGoogle Scholar
  15. Ballas N, Lioy DT, Grunseich C, Mandel G (2009) Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat Neurosci 12(3):311–317PubMedCrossRefGoogle Scholar
  16. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21(3):381–395PubMedCrossRefGoogle Scholar
  17. Bartholdi D, Roelfsema JH, Papadia F, Breuning MH, Niedrist D, Hennekam RC, Schinzel A, Peters DJ (2007) Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300. J Med Genet 44(5):327–333PubMedCrossRefGoogle Scholar
  18. Bartsch O, Labonte J, Albrecht B, Wieczorek D, Lechno S, Zechner U, Haaf T (2010) Two patients with EP300 mutations and facial dysmorphism different from the classic Rubinstein-Taybi syndrome. Am J Med Genet 152A:181–184PubMedCrossRefGoogle Scholar
  19. Basel-Vanagaite L (2010) Acute lymphoblastic leukemia in Weaver syndrome. Am J Med Genet 152A:383–386PubMedCrossRefGoogle Scholar
  20. Batenburg NL, Mitchell TR, Leach DM, Rainbow AJ, Zhu XD (2012) Cockayne Syndrome group B protein interacts with TRF2 and regulates telomere length and stability. Nucleic Acids Res 40(19):9661–9674PubMedCrossRefGoogle Scholar
  21. Baujat G, Rio M, Rossignol S, Sanlaville D, Lyonnet S, Le Merrer M, Munnich A, Gicquel C, Cormier-Daire V, Colleaux L (2004) Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome. Am J Hum Genet 74:715–720PubMedCrossRefGoogle Scholar
  22. Berdasco M, Esteller M (2010) Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev Cell 19(5):698–711PubMedCrossRefGoogle Scholar
  23. Berdasco M, Esteller M (2011) DNA methylation in stem cell renewal and multipotency. Stem Cell Res Ther 2(5):42PubMedCrossRefGoogle Scholar
  24. Berdasco M, Ropero S, Setien F, Fraga MF, Lapunzina P, Losson R, Alaminos M, Cheung NK, Rahman N, Esteller M (2009) Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma. Proc Natl Acad Sci USA 106(51):21830–21835PubMedCrossRefGoogle Scholar
  25. Berquist BR, Canugovi C, Sykora P, Wilson DM 3rd, Bohr VA (2012) Human Cockayne syndrome B protein reciprocally communicates with mitochondrial proteins and promotes transcriptional elongation. Nucleic Acids Res 40(17):8392–8405PubMedCrossRefGoogle Scholar
  26. Bourtchouladze R, Lidge R, Catapano R, Stanley J, Gossweiler S, Romashko D, Scott R, Tully T (2003) A mouse model of Rubinstein-Taybi syndrome: defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4. Proc Natl Acad Sci USA 100:10518–10522PubMedCrossRefGoogle Scholar
  27. Brun ME, Lana E, Rivals I, Lefranc G, Sarda P, Claustres M, Mégarbané A, De Sario A (2011) Heterochromatic genes undergo epigenetic changes and escape silencing in immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome. PLoS ONE 6(4):e19464PubMedCrossRefGoogle Scholar
  28. Campeau PM, Kim JC, Lu JT, Schwartzentruber JA, Abdul-Rahman OA, Schlaubitz S, Murdock DM, Jiang MM, Lammer EJ, Enns GM, Rhead WJ, Rowland J, Robertson SP, Cormier-Daire V, Bainbridge MN, Yang XJ, Gingras MC, Gibbs RA, Rosenblatt DS, Majewski J, Lee BH (2012a) Mutations in KAT6B, encoding a histone acetyltransferase, cause Genitopatellar syndrome. Am J Hum Genet 90(2):282–289PubMedCrossRefGoogle Scholar
  29. Campeau PM, Lu JT, Dawson BC, Fokkema IF, Robertson SP, Gibbs RA, Lee BH (2012b) The KAT6B-related disorders genitopatellar syndrome and Ohdo/SBBYS syndrome have distinct clinical features reflecting distinct molecular mechanisms. Hum Mutat 33(11):1520–1525PubMedCrossRefGoogle Scholar
  30. Carney RM, Wolpert CM, Ravan SA, Shahbazian M, Ashley-Koch A, Cuccaro ML, Vance JM, Pericak-Vance MA (2003) Identification of MeCP2 mutations in a series of females with autistic disorder. Pediat Neurol 28:205–211PubMedCrossRefGoogle Scholar
  31. 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(5880):1224–1229PubMedCrossRefGoogle Scholar
  32. Champagne N, Bertos NR, Pelletier N, Wang AH, Vezmar M, Yang Y, Heng HH, Yang XJ (1999) Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein. J Biol Chem 274:28528–28536PubMedCrossRefGoogle Scholar
  33. Chan HM, La Thangue NB (2001) p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci 114:2363–2373PubMedGoogle Scholar
  34. Chang Q, Khare G, Dani V, Nelson S, Jaenisch R (2006) The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49(3):341–348PubMedCrossRefGoogle Scholar
  35. Chapnik E, Sasson V, Blelloch R, Hornstein E (2012) Dgcr8 controls neural crest cells survival in cardiovascular development. Dev Biol 362(1):50–56PubMedCrossRefGoogle Scholar
  36. Chen B, Cepko CL (2009) HDAC4 regulates neuronal survival in normal and diseased retinas. Science 323(5911):256–259PubMedCrossRefGoogle Scholar
  37. Chen JF, Murchison EP, Tang R, Callis TE, Tatsuguchi M, Deng Z, Rojas M, Hammond SM, Schneider MD, Selzman CH, Meissner G, Patterson C, Hannon GJ, Wang DZ (2008) Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc Natl Acad Sci USA 105(6):2111–2116PubMedCrossRefGoogle Scholar
  38. Chen H, Gu X, Su IH, Bottino R, Contreras JL, Tarakhovsky A, Kim SK (2009) Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus. Genes Dev 23(8):975–985PubMedCrossRefGoogle Scholar
  39. Chen YC, Gatchel JR, Lewis RW, Mao CA, Grant PA, Zoghbi HY, Dent SY (2012a) Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model. Hum Mol Genet 21(2):394–405PubMedCrossRefGoogle Scholar
  40. Chen Z, Wu J, Yang C, Fan P, Balazs L, Jiao Y, Lu M, Gu W, Li C, Pfeffer LM, Tigyi G, Yue J (2012b) DiGeorge syndrome critical region 8 (DGCR8) protein-mediated microRNA biogenesis is essential for vascular smooth muscle cell development in mice. J Biol Chem 287(23):19018–19028PubMedCrossRefGoogle Scholar
  41. Chou RH, Yu YL, Hung MC (2011) The roles of EZH2 in cell lineage commitment. Am J Transl Res 3(3):243–250PubMedGoogle Scholar
  42. Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365:855–859PubMedCrossRefGoogle Scholar
  43. Claes S, Devriendt K, Van Goethem G, Roelen L, Meireleire J, Raeymaekers P, Cassiman JJ, Fryns JP (2000) Novel syndromic form of X-linked complicated spastic paraplegia. Am J Med Genet 94:1–4PubMedCrossRefGoogle Scholar
  44. Clayton-Smith J, O’Sullivan J, Daly S, Bhaskar S, Day R, Anderson B, Voss AK, Thomas T, Biesecker LG, Smith P, Fryer A, Chandler KE, Kerr B, Tassabehji M, Lynch SA, Krajewska-Walasek M, McKee S, Smith J, Sweeney E, Mansour S, Mohammed S, Donnai D, Black G (2011) Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome. Am J Hum Genet 89:675–681PubMedCrossRefGoogle Scholar
  45. 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(21):2679–2689PubMedCrossRefGoogle Scholar
  46. Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10(10):704–714PubMedCrossRefGoogle Scholar
  47. Das C, Lucia MS, Hansen KC, Tyler JK (2009) CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature 459(7243):113–117PubMedCrossRefGoogle Scholar
  48. Day JJ, Sweatt JD (2012) Epigenetic treatments for cognitive impairments. Neuropsychopharmacology 37(1):247–260PubMedCrossRefGoogle Scholar
  49. De Felice C, Signorini C, Leoncini S, Pecorelli A, Durand T, Valacchi G, Ciccoli L, Hayek J (2012) The role of oxidative stress in Rett syndrome: an overview. Ann N Y Acad Sci 1259(1):121–135PubMedCrossRefGoogle Scholar
  50. De Greef JC, Wang J, Balog J, den Dunnen JT, Frants RR, Straasheijm KR, Aytekin C, van der Burg M, Duprez L, Ferster A, Gennery AR, Gimelli G, Reisli I, Schuetz C, Schulz A, Smeets DF, Sznajer Y, Wijmenga C, van Eggermond MC, van Ostaijen-Ten Dam MM, Lankester AC, van Tol MJ, van den Elsen PJ, Weemaes CM, van der Maarel SM (2011) Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. Am J Hum Genet 88(6):796–804PubMedCrossRefGoogle Scholar
  51. Dillon SC, Zhang X, Trievel RC, Cheng X (2005) The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol 6(8):227PubMedCrossRefGoogle Scholar
  52. Douglas J, Hanks S, Temple IK, Davies S, Murray A, Upadhyaya M, Tomkins S, Hughes HE, Cole TR, Rahman N (2003) NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes. Am J Hum Genet 72(1):132–143PubMedCrossRefGoogle Scholar
  53. Ea CK, Hao S, Yeo KS, Baltimore D (2012) EHMT1 binds to NF-κB p50 and represses gene expression. J Biol Chem 287(37):31207–31217PubMedCrossRefGoogle Scholar
  54. Eckner R, Ewen ME, Newsome D, Gerdes M, DeCaprio JA, Lawrence JB, Livingston DM (1994) Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev 8:869–884PubMedCrossRefGoogle Scholar
  55. Edbauer D, Neilson JR, Foster KA, Wang CF, Seeburg DP, Batterton MN, Tada T, Dolan BM, Sharp PA, Sheng M (2010) Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron 65(3):373–384PubMedCrossRefGoogle Scholar
  56. Ehrlich M (2003) The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease. Clin Immunol 109:17–28PubMedCrossRefGoogle Scholar
  57. Eissenberg JC, Wong M, Chrivia JC (2005) Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway. Mol Cell Biol 25(15):6559–6569PubMedCrossRefGoogle Scholar
  58. Erdel F, Rippe K (2011) Chromatin remodelling in mammalian cells by ISWI-type complexes–where, when and why? FEBS J 278(19):3608–3618PubMedCrossRefGoogle Scholar
  59. Esteller M (2008) Epigenetics in cancer. N Engl J Med 358(11):1148–1159PubMedCrossRefGoogle Scholar
  60. Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12(12):861–874PubMedCrossRefGoogle Scholar
  61. Etchegaray JP, Yang X, DeBruyne JP, Peters AH, Weaver DR, Jenuwein T, Reppert SM (2006) The polycomb group protein EZH2 is required for mammalian circadian clock function. J Biol Chem 281(30):21209–21215PubMedCrossRefGoogle Scholar
  62. Fatemi M, Hermann A, Pradhan S, Jeltsch A (2001) The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA. J Mol Biol 309(5):1189–1199PubMedCrossRefGoogle Scholar
  63. Feng J, Zhou Y, Campbell SL, Le T, Li E, Sweatt JD, Silva AJ, Fan G (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13(4):423–430PubMedCrossRefGoogle Scholar
  64. Fernandez AG, Gunsalus KC, Huang J, Chuang LS, Ying N, Liang HL, Tang C, Schetter AJ, Zegar C, Rual JF, Hill DE, Reinke V, Vidal M, Piano F (2005) New genes with roles in the C. elegans embryo revealed using RNAi of ovary-enriched ORFeome clones. Genome Res 15(2):250–259PubMedCrossRefGoogle Scholar
  65. Fiskus W, Wang Y, Joshi R, Rao R, Yang Y, Chen J, Kolhe R, Balusu R, Eaton K, Lee P, Ustun C, Jillella A, Buser CA, Peiper S, Bhalla K (2008) Cotreatment with vorinostat enhances activity of MK-0457 (VX-680) against acute and chronic myelogenous leukemia cells. Clin Cancer Res 14(19):6106–6115PubMedCrossRefGoogle Scholar
  66. Flaus A, Owen-Hughes T (2011) Mechanisms for ATP-dependent chromatin remodelling: the means to the end. FEBS J 278(19):3579–3595PubMedCrossRefGoogle Scholar
  67. Franklin TB, Mansuy IM (2011) The involvement of epigenetic defects in mental retardation. Neurobiol Learn Mem 96(1):61–67PubMedCrossRefGoogle Scholar
  68. Froyen G, Bauters M, Voet T, Marynen P (2006) X-linked mental retardation and epigenetics. J Cell Mol Med 10(4):808–825PubMedCrossRefGoogle Scholar
  69. Garden GA, La Spada AR (2008) Molecular pathogenesis and cellular pathology of spinocerebellar ataxia type 7 neurodegeneration. Cerebellum 7(2):138–149PubMedCrossRefGoogle Scholar
  70. Giacometti E, Luikenhuis S, Beard C, Jaenisch R (2007) Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc Natl Acad Sci USA 104(6):1931–1936PubMedCrossRefGoogle Scholar
  71. 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 80:837–845PubMedCrossRefGoogle Scholar
  72. 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 24:368–371PubMedCrossRefGoogle Scholar
  73. Gibbons RJ, Pellagatti A, Garrick D, Wood WG, Malik N, Ayyub H, Langford C, Boultwood J, Wainscoat JS, Higgs DR (2003) Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS). Nat Genet 34:446–449PubMedCrossRefGoogle Scholar
  74. Gibson WT, Hood RL, Zhan SH, Bulman DE, Fejes AP, Moore R, Mungall AJ, Eydoux P, Babul-Hirji R, An J, Marra MA, FORGE Canada Consortium, Chitayat D, Boycott KM, Weaver DD, Jones SJM (2012) Mutations in EZH2 cause Weaver syndrome. Am J Hum Genet 90:110–118PubMedCrossRefGoogle Scholar
  75. Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S, Dewell S, Law M, Guo X, Li X, Wen D, Chapgier A, DeKelver RC, Miller JC, Lee YL, Boydston EA, Holmes MC, Gregory PD, Greally JM, Rafii S, Yang C, Scambler PJ, Garrick D, Gibbons RJ, Higgs DR, Cristea IM, Urnov FD, Zheng D (2010) Allis CD (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140(5):678–691PubMedCrossRefGoogle Scholar
  76. Goodship J, Cross I, LiLing J, Wren C (1998) A population study of chromosome 22q11 deletions in infancy. Arch Dis Child 79:348–351PubMedCrossRefGoogle Scholar
  77. Guy J, Gan J, Selfridge J, Cobb S, Bird A (2007) Reversal of neurological defects in a mouse model of Rett syndrome. Science 315(5815):1143–1147PubMedCrossRefGoogle Scholar
  78. Hallam TM, Bourtchouladze R (2006) Rubinstein-Taybi syndrome: molecular findings and therapeutic approaches to improve cognitive dysfunction. Cell Mol Life Sci 63:1725–1735PubMedCrossRefGoogle Scholar
  79. Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN (2006) Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 125(5):887–901PubMedCrossRefGoogle Scholar
  80. Hannibal MC, Buckingham KJ, Ng SB, Ming JE, Beck AE, McMillin MJ, Gildersleeve HI, Bigham AW, Tabor HK, Mefford HC, Cook J, Yoshiura K, Matsumoto T, Matsumoto N, Miyake N, Tonoki H, Naritomi K, Kaname T, Nagai T, Ohashi H, Kurosawa K, Hou JW, Ohta T, Liang D, Sudo A, Morris CA, Banka S, Black GC, Clayton-Smith J, Nickerson DA, Zackai EH, Shaikh TH, Donnai D, Niikawa N, Shendure J, Bamshad MJ (2011) Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome. Am J Med Genet 155A:1511–1516PubMedCrossRefGoogle Scholar
  81. Hargreaves DC, Crabtree GR (2011) ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res 21(3):396–420PubMedCrossRefGoogle Scholar
  82. Harikrishnan KN, Chow MZ, Baker EK, Pal S, Bassal S, Brasacchio D, Wang L, Craig JM, Jones PL, Sif S, El-Osta A (2005) Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing. Nat Genet 37:254–264PubMedCrossRefGoogle Scholar
  83. Helmlinger D, Hardy S, Abou-Sleymane G, Eberlin A, Bowman AB, Gansmüller A, Picaud S, Zoghbi HY, Trottier Y, Tora L, Devys D (2006) Glutamine-expanded ataxin-7 alters TFTC/STAGA recruitment and chromatin structure leading to photoreceptor dysfunction. PLoS Biol 4(3):e67PubMedCrossRefGoogle Scholar
  84. Hennekam RCM (2006) Rubinstein-Taybi syndrome. Europ. J Hum Genet 14:981–985CrossRefGoogle Scholar
  85. Henning KA, Li L, Iyer N, McDaniel LD, Reagan MS, Legerski R, Schultz RA, Stefanini M, Lehmann AR, Mayne LV, Friedberg EC (1995) The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH. Cell 82:555–564PubMedCrossRefGoogle Scholar
  86. Herman D, Jenssen K, Burnett R, Soragni E, Perlman SL, Gottesfeld JM (2006) Histone deacetylase inhibitors reverse gene silencing in Friedreich’s ataxia. Nat Chem Biol 2(10):551–558PubMedCrossRefGoogle Scholar
  87. Heyn H, Esteller M (2012) DNA methylation profiling in the clinic: applications and challenges. Nat Rev Genet 13(10):679–692PubMedCrossRefGoogle Scholar
  88. Heyn H, Vidal E, Sayols S, Sanchez-Mut JV, Moran S, Medina I, Sandoval J, Simó-Riudalbas L, Szczesna K, Huertas D, Gatto S, Matarazzo MR, Dopazo J, Esteller M (2012) Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient. Epigenetics 7(6):542–550PubMedCrossRefGoogle Scholar
  89. Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ (2009) DICER1 mutations in familial pleuropulmonary blastoma. Science 325:965PubMedCrossRefGoogle Scholar
  90. Ho L, Crabtree GR (2010) Chromatin remodelling during development. Nature 463(7280):474–484PubMedCrossRefGoogle Scholar
  91. Ho L, Jothi R, Ronan JL, Cui K, Zhao K, Crabtree GR (2009) An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network. Proc Natl Acad Sci USA 106(13):5187–5191PubMedCrossRefGoogle Scholar
  92. 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(4):2041–2046PubMedCrossRefGoogle Scholar
  93. Hong S, Cho YW, Yu LR, Yu H, Veenstra TD, Ge K (2007) Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc Natl Acad Sci USA 104(47):18439–18444PubMedCrossRefGoogle Scholar
  94. Hood RL, Lines MA, Nikkel SM, Schwartzentruber J, Beaulieu C, Nowaczyk MJ, Allanson J, Kim CA, Wieczorek D, Moilanen JS, Lacombe D, Gillessen-Kaesbach G, Whiteford ML, Quaio CR, Gomy I, Bertola DR, Albrecht B, Platzer K, McGillivray G, Zou R, McLeod DR, Chudley AE, Chodirker BN, Marcadier J, FORGE Canada Consortium, Majewski J, Bulman DE, White SM, Boycott KM (2012) Mutations in SRCAP, encoding SNF2-related CREBBP activator protein, cause Floating-Harbor syndrome. Am J Hum Genet 90(2):308–313PubMedCrossRefGoogle Scholar
  95. 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(1):31–40PubMedGoogle Scholar
  96. 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(12):3398–3412PubMedCrossRefGoogle Scholar
  97. Hurd EA, Poucher HK, Cheng K, Raphael Y, Martin DM (2010) The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear. Development 137(18):3139–3150PubMedCrossRefGoogle Scholar
  98. Ishibashi T, Thambirajah AA, Ausió J (2008) MeCP2 preferentially binds to methylated linker DNA in the absence of the terminal tail of histone H3 and independently of histone acetylation. FEBS Lett 582(7):1157–1162PubMedCrossRefGoogle Scholar
  99. Jensen LR, Amende M, Gurok U, Moser B, Gimmel V, Tzschach A, Janecke AR, Tariverdian G, Chelly J, Fryns JP, Van Esch H, Kleefstra T, Hamel B, Moraine C, Gecz J, Turner G, Reinhardt R, Kalscheuer VM, Ropers HH, Lenzner S (2005) Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation. Am J Hum Genet 76:227–236PubMedCrossRefGoogle Scholar
  100. Jiang X, Zhou Y, Xian L, Chen W, Wu H, Gao X (2012) The mutation in Chd7 causes misexpression of Bmp4 and developmental defects in telencephalic midline. Am J Pathol 181(2):626–641PubMedCrossRefGoogle Scholar
  101. 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(5):690–709PubMedCrossRefGoogle Scholar
  102. Jin Q, Yu LR, Wang L, Zhang Z, Kasper LH, Lee JE, Wang C, Brindle PK, Dent SY, Ge K (2011) Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation. EMBO J 30(2):249–262PubMedCrossRefGoogle Scholar
  103. 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(2):187–191PubMedCrossRefGoogle Scholar
  104. Josefowicz SZ, Wilson CB, Rudensky AY (2009) Cutting edge: TCR stimulation is sufficient for induction of Foxp3 expression in the absence of DNA methyltransferase 1. J Immunol 182(11):6648–6652PubMedCrossRefGoogle Scholar
  105. Juan AH, Derfoul A, Feng X, Ryall JG, Dell’Orso S, Pasut A, Zare H, Simone JM, Rudnicki MA, Sartorelli V (2011) Polycomb EZH2 controls self-renewal and safeguards the transcriptional identity of skeletal muscle stem cells. Genes Dev 25(8):789–794PubMedCrossRefGoogle Scholar
  106. Kaminskas E, Farrell A, Abraham S, Baird A, Hsieh LS, Lee SL, Leighton JK, Patel H, Rahman A, Sridhara R, Wang YC, Pazdur R (2005) FDA, Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res 11(10):3604–3608PubMedCrossRefGoogle Scholar
  107. Kasper LH, Thomas MC, Zambetti GP, Brindle PK (2011) Double null cells reveal that CBP and p300 are dispensable for p53 targets p21 and Mdm2 but variably required for target genes of other signaling pathways. Cell Cycle 10(2):212–221PubMedCrossRefGoogle Scholar
  108. Kawahara Y, Mieda-Sato A (2012) TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc Natl Acad Sci USA 109(9):3347–3352PubMedCrossRefGoogle Scholar
  109. Kazantsev AG, Thompson LM (2008) Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov 7(10):854–868PubMedCrossRefGoogle Scholar
  110. Kilgore M, Miller CA, Fass DM, Hennig KM, Haggarty SJ, Sweatt JD, Rumbaugh G (2010) Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology 35(4):870–880PubMedCrossRefGoogle Scholar
  111. 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 83:511–519PubMedCrossRefGoogle Scholar
  112. Kirmizis A, Bartley SM, Kuzmichev A, Margueron R, Reinberg D, Green R, Farnham PJ (2004) Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Genes Dev 18(13):1592–1605PubMedCrossRefGoogle Scholar
  113. Kleefstra T, van Zelst-Stams WA, Nillesen WM, Cormier-Daire V, Houge G, Foulds N, van Dooren M, Willemsen MH, Pfundt R, Turner A, Wilson M, McGaughran J, Rauch A, Zenker M, Adam MP, Innes M, Davies C, López AG, Casalone R, Weber A, Brueton LA, Navarro AD, Bralo MP, Venselaar H, Stegmann SP, Yntema HG, van Bokhoven H, Brunner HG (2009) Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype. J Med Genet 46:598–606PubMedCrossRefGoogle Scholar
  114. Kleefstra T, Brunner HG, Amiel J, Oudakker AR, Nillesen WM, Magee A, Geneviève D, Cormier-Daire V, van Esch H, Fryns JP, Hamel BC, Sistermans EA, de Vries BB, van Bokhoven H (2006) Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome. Am J Hum Genet 79:370–377PubMedCrossRefGoogle Scholar
  115. Kleefstra T, Kramer JM, Neveling K, Willemsen MH, Koemans TS, Vissers LE, Wissink-Lindhout W, Fenckova M, van den Akker WM, Kasri NN, Nillesen WM, Prescott T, Clark RD, Devriendt K, van Reeuwijk J, de Brouwer AP, Gilissen C, Zhou H, Brunner HG, Veltman JA, Schenck A, van Bokhoven H (2012) Disruption of an EHMT1-Associated Chromatin-Modification Module Causes Intellectual Disability. Am J Hum Genet 91(1):73–82PubMedGoogle Scholar
  116. Klein CJ, Botuyan MV, Wu Y, Ward CJ, Nicholson GA, Hammans S, Hojo K, Yamanishi H, Karpf AR, Wallace DC, Simon M, Lander C, Boardman LA, Cunningham JM, Smith GE, Litchy WJ, Boes B, Atkinson EJ, Middha S, Dyck B, Parisi JE, Mer G, Smith DI, Dyck PJ (2011) Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet 43:595–600PubMedCrossRefGoogle Scholar
  117. Kleine-Kohlbrecher D, Christensen J, Vandamme J, Abarrategui I, Bak M, Tommerup N, Shi X, Gozani O, Rappsilber J, Salcini AE, Helin K (2010) A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation. Mol Cell 38(2–2):165–178PubMedCrossRefGoogle Scholar
  118. Koivisto AM, Ala-Mello S, Lemmelä S, Komu HA, Rautio J, Järvelä I (2007) Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate. Clin Genet 72:145–149PubMedCrossRefGoogle Scholar
  119. Korzus E, Rosenfeld MG, Mayford M (2004) CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 42:961–972PubMedCrossRefGoogle Scholar
  120. 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(3):901–907PubMedCrossRefGoogle Scholar
  121. Kraft M, Cirstea IC, Voss AK, Thomas T, Goehring I, Sheikh BN, Gordon L, Scott H, Smyth GK, Ahmadian MR, Trautmann U, Zenker M, Tartaglia M, Ekici A, Reis A, Dörr HG, Rauch A, Thiel CT (2011) Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice. J Clin Invest 121(9):3479–3491PubMedCrossRefGoogle Scholar
  122. Kramer JM, van Bokhoven H (2009) Genetic and epigenetic defects in mental retardation. Int J Biochem Cell Biol 41(1):96–107PubMedCrossRefGoogle Scholar
  123. Kramer JM, Kochinke K, Oortveld MA, Marks H, Kramer D, de Jong EK, Asztalos Z, Westwood JT, Stunnenberg HG, Sokolowski MB, Keleman K, Zhou H, van Bokhoven H, Schenck A (2011) Epigenetic regulation of learning and memory by Drosophila EHMT/G9a. PLoS Biol 9(1):e1000569PubMedCrossRefGoogle Scholar
  124. 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(2):197–204PubMedCrossRefGoogle Scholar
  125. 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(4):365–366PubMedCrossRefGoogle Scholar
  126. Lacombe D, Saura R, Taine L, Battin J (1992) Confirmation of assignment of a locus for Rubinstein-Taybi syndrome gene to 16p13.3. Am J Med Gent 44:126–128CrossRefGoogle Scholar
  127. Lagier-Tourenne C, Polymenidou M, Cleveland DW (2010) TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum Mol Genet 19(R1):R46–R64PubMedCrossRefGoogle Scholar
  128. Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y (2007) A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449(7163):689–694PubMedCrossRefGoogle Scholar
  129. Lana E, Mégarbané A, Tourrière H, Sarda P, Lefranc G, Claustres M, De Sario A (2012) DNA replication is altered in Immunodeficiency Centromeric instability Facial anomalies (ICF) cells carrying DNMT3B mutations. Eur J Hum Genet 20(10):1044–1050PubMedCrossRefGoogle Scholar
  130. Lapunzina P (2005) Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am J Med Genet C Semin Med Genet 137C(1):53–71PubMedCrossRefGoogle Scholar
  131. Laugel V, Dalloz C, Durand M, Sauvanaud F, Kristensen U, Vincent MC, Pasquier L, Odent S, Cormier-Daire V, Gener B, Tobias ES, Tolmie JL, Martin-Coignard D, Drouin-Garraud V, Heron D, Journel H, Raffo E, Vigneron J, Lyonnet S, Murday V, Gubser-Mercati D, Funalot B, Brueton L, Sanchez Del Pozo J, Muñoz E, Gennery AR, Salih M, Noruzinia M, Prescott K, Ramos L, Stark Z, Fieggen K, Chabrol B, Sarda P, Edery P, Bloch-Zupan A, Fawcett H, Pham D, Egly JM, Lehmann AR, Sarasin A, Dollfus H (2010) Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Hum Mutat 31(2):113–126PubMedCrossRefGoogle Scholar
  132. Laumonnier F, Holbert S, Ronce N, Faravelli F, Lenzner S, Schwartz CE, Lespinasse J, Van Esch H, Lacombe D, Goizet C, Phan-Dinh Tuy F, van Bokhoven H, Fryns JP, Chelly J, Ropers HH, Moraine C, Hamel BC, Briault S (2005) Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate. J Med Genet 42:780–786PubMedCrossRefGoogle Scholar
  133. Law MJ, Lower KM, Voon HP, Hughes JR, Garrick D, Viprakasit V, Mitson M, De Gobbi M, Marra M, Morris A, Abbott A, Wilder SP, Taylor S, Santos GM, Cross J, Ayyub H, Jones S, Ragoussis J, Rhodes D, Dunham I, Higgs DR, Gibbons RJ (2010) ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner. Cell 143:367–378PubMedCrossRefGoogle Scholar
  134. Layman WS, McEwen DP, Beyer LA, Lalani SR, Fernbach SD, Oh E, Swaroop A, Hegg CC, Raphael Y, Martens JR, Martin DM (2009) Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome. Hum Mol Genet 18(11):1909–1923PubMedCrossRefGoogle Scholar
  135. Lederer D, Grisart B, Digilio MC, Benoit V, Crespin M, Ghariani SC, Maystadt I, Dallapiccola B, Verellen-Dumoulin C (2012) Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. Am J Hum Genet 90:119–124PubMedCrossRefGoogle Scholar
  136. Lessard J, Wu JI, Ranish JA, Wan M, Winslow MM, Staahl BT, Wu H, Aebersold R, Graef IA, Crabtree GR (2007) An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron 55(2):201–215PubMedCrossRefGoogle Scholar
  137. Lewis PW, Elsaesser SJ, Noh KM, Stadler SC, Allis CD (2010) Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc Natl Acad Sci USA 107(32):14075–14080PubMedCrossRefGoogle Scholar
  138. Li H, Zhong X, Chau KF, Williams EC, Chang Q (2011) Loss of activity-induced phosphorylation of MeCP2 enhances synaptogenesis. LTP and spatial memory. Nat Neurosci 14(8):1001–1008CrossRefGoogle Scholar
  139. Licht CL, Stevnsner T, Bohr VA (2003) Cockayne syndrome group B cellular and biochemical functions. Am J Hum Genet 73:1217–1239PubMedCrossRefGoogle Scholar
  140. Ling SC, Albuquerque CP, Han JS, Lagier-Tourenne C, Tokunaga S, Zhou H, Cleveland DW (2010) ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS. Proc Natl Acad Sci USA 107(30):13318–13323PubMedCrossRefGoogle Scholar
  141. Lioy DT, Garg SK, Monaghan CE, Raber J, Foust KD, Kaspar BK, Hirrlinger PG, Kirchhoff F, Bissonnette JM, Ballas N, Mandel G (2011) A role for glia in the progression of Rett’s syndrome. Nature 475(7357):497–500PubMedCrossRefGoogle Scholar
  142. Liu L, van Groen T, Kadish I, Tollefsbol TO (2009) DNA methylation impacts on learning and memory in aging. Neurobiol Aging 30(4):549–560PubMedCrossRefGoogle Scholar
  143. Liu W, Tanasa B, Tyurina OV, Zhou TY, Gassmann R, Liu WT, Ohgi KA, Benner C, Garcia-Bassets I, Aggarwal AK, Desai A, Dorrestein PC, Glass CK, Rosenfeld MG (2010) PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression. Nature 466(7305):508–512PubMedCrossRefGoogle Scholar
  144. Lopez-Atalaya JP, Gervasini C, Mottadelli F, Spena S, Piccione M, Scarano G, Selicorni A, Barco A, Larizza L (2012) Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein-Taybi syndrome. J Med Genet 49(1):66–74PubMedCrossRefGoogle Scholar
  145. 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(1):46–51PubMedCrossRefGoogle Scholar
  146. Macrae IJ, Zhou K, Li F, Repic A, Brooks AN, Cande WZ, Adams PD, Doudna JA (2006) Structural basis for double-stranded RNA processing by Dicer. Science 311(5758):195–198PubMedCrossRefGoogle Scholar
  147. Mayo S, Garin I, Monfort S, Roselló M, Orellana C, Oltra S, Zazo C, de Naclares GP, Martínez F (2012) Hypomethylation of the KCNQ1OT1 imprinting center of chromosome 11 associated to Sotos-like features. J Hum Genet 57(2):153–156PubMedCrossRefGoogle Scholar
  148. McMahon SJ, Pray-Grant MG, Schieltz D, Yates JR 3rd, Grant PA (2005) Polyglutamine-expanded spinocerebellar ataxia-7 protein disrupts normal SAGA and SLIK histone acetyltransferase activity. Proc Natl Acad Sci USA 102(24):8478–8482PubMedCrossRefGoogle Scholar
  149. McManus KJ, Hendzel MJ (2003) Quantitative analysis of CBP- and P300-induced histone acetylations in vivo using native chromatin. Mol Cell Biol 23(21):7611–7627PubMedCrossRefGoogle Scholar
  150. Merson TD, Dixon MP, Collin C, Rietze RL, Bartlett PF, Thomas T, Voss AK (2006) The transcriptional coactivator Querkopf controls adult neurogenesis. J Neurosci 26(44):11359–11370PubMedCrossRefGoogle Scholar
  151. Miska EA, Langley E, Wolf D, Karlsson C, Pines J, Kouzarides T (2001) Differential localization of HDAC4 orchestrates muscle differentiation. Nucleic Acids Res 29(16):3439–3447PubMedCrossRefGoogle Scholar
  152. Monroy MA, Ruhl DD, Xu X, Granner DK, Yaciuk P, Chrivia JC (2001) Regulation of cAMP-responsive element-binding protein-mediated transcription by the SNF2/SWI-related protein. SRCAP. J Biol Chem 276(44):40721–40726CrossRefGoogle Scholar
  153. Moretti P, Zoghbi HY (2006) MeCP2 dysfunction in Rett syndrome and related disorders. Curr Opin Genet Dev 16(3):276–281PubMedCrossRefGoogle Scholar
  154. Morris B, Etoubleau C, Bourthoumieu S, Reynaud-Perrine S, Laroche C, Lebbar A, Yardin C, Elsea SH (2012) Dose dependent expression of HDAC4 causes variable expressivity in a novel inherited case of brachydactyly mental retardation syndrome. Am J Med Genet A 158A(8):2015–2020PubMedCrossRefGoogle Scholar
  155. Morrison AJ, Shen X (2009) Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes. Nat Rev Mol Cell Biol 10(6):373–384PubMedCrossRefGoogle Scholar
  156. 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(7322):443–446PubMedCrossRefGoogle Scholar
  157. Murawska M, Brehm A (2011) CHD chromatin remodelers and the transcription cycle. Transcription 2(6):244–253PubMedCrossRefGoogle Scholar
  158. Na ES, Nelson ED, Kavalali ET, Monteggia LM (2012) The Impact of MeCP2 Loss- or Gain-of-Function on Synaptic Plasticity. Neuropsychopharmacology. doi:10.1038/npp.2012.116 PubMedGoogle Scholar
  159. Nagl NG Jr, Wang X, Patsialou A, Van Scoy M, Moran E (2007) Distinct mammalian SWI/SNF chromatin remodeling complexes with opposing roles in cell-cycle control. EMBO J 26(3):752–763PubMedCrossRefGoogle Scholar
  160. Nakamura Y, Tagawa K, Oka T, Sasabe T, Ito H, Shiwaku H, La Spada AR, Okazawa H (2012) Ataxin-7 associates with microtubules and stabilizes the cytoskeletal network. Hum Mol Genet 21(5):1099–1110PubMedCrossRefGoogle Scholar
  161. 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 Nat Acad Sci USA 104:2709–2714PubMedCrossRefGoogle Scholar
  162. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133PubMedCrossRefGoogle Scholar
  163. 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(25):9613–9618PubMedCrossRefGoogle Scholar
  164. Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J (2010) Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet 42:790–793PubMedCrossRefGoogle Scholar
  165. Nguyen MV, Du F, Felice CA, Shan X, Nigam A, Mandel G, Robinson JK, Ballas N (2012) MeCP2 Is Critical for Maintaining Mature Neuronal Networks and Global Brain Anatomy during Late Stages of Postnatal Brain Development and in the Mature Adult Brain. J Neurosci 32(29):10021–10034PubMedCrossRefGoogle Scholar
  166. Nielsen AL, Jørgensen P, Lerouge T, Cerviño M, Chambon P, Losson R (2004) Nizp1, a novel multitype zinc finger protein that interacts with the NSD1 histone lysine methyltransferase through a unique C2HR motif. Mol Cell Biol 24(12):5184–5196PubMedCrossRefGoogle Scholar
  167. Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T (1981) Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediat 99:565–569PubMedCrossRefGoogle Scholar
  168. Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y (2002) A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science 296(5570):1132–1136PubMedCrossRefGoogle Scholar
  169. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y (1996) The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87:953–959PubMedCrossRefGoogle Scholar
  170. Ounap K, Puusepp-Benazzouz H, Peters M, Vaher U, Rein R, Proos A, Field M, Reimand T (2012) A novel c.2T > C mutation of the KDM5C/JARID1C gene in one large family with X-linked intellectual disability. Eur J Med Genet 55(3):178–184PubMedCrossRefGoogle Scholar
  171. Park JH, Park EJ, Lee HS, Kim SJ, Hur SK, Imbalzano AN, Kwon J (2006) Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction. EMBO J 25(17):3986–3997PubMedCrossRefGoogle Scholar
  172. Pasillas MP, Shah M, Kamps MP (2011) NSD1 PHD domains bind methylated H3K4 and H3K9 using interactions disrupted by point mutations in human Sotos syndrome. Hum Mutat 32(3):292–298PubMedCrossRefGoogle Scholar
  173. Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, Masuno M, Tommerup N, van Ommen GJ, Goodman RH, Peters DJ (1995) Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376(6538):348–351PubMedCrossRefGoogle Scholar
  174. Picketts DJ, Higgs DR, Bachoo S, Blake DJ, Quarrell OW, Gibbons RJ (1996) ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome. Hum Molec Genet 5:1899–1907PubMedCrossRefGoogle Scholar
  175. Portela A, Esteller M (2010) Epigenetic modifications and human disease. Nat Biotechnol 28(10):1057–1068PubMedCrossRefGoogle Scholar
  176. Qi HH, Sarkissian M, Hu GQ, Wang Z, Bhattacharjee A, Gordon DB, Gonzales M, Lan F, Ongusaha PP, Huarte M, Yaghi NK, Lim H, Garcia BA, Brizuela L, Zhao K, Roberts TM, Shi Y (2010) Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature 466(7305):503–507PubMedCrossRefGoogle Scholar
  177. Qiao Y, Liu X, Harvard C, Hildebrand MJ, Rajcan-Separovic E, Holden JJ, Lewis ME (2008) Autism-associated familial microdeletion of Xp11.22. Clin Genet 74(2):134–144PubMedCrossRefGoogle Scholar
  178. Rahman N (2005) Mechanisms predisposing to childhood overgrowth and cancer. Curr Opin Genet Dev 15(3):227–233PubMedCrossRefGoogle Scholar
  179. Rajan I, Savelieva KV, Ye GL, Wang CY, Malbari MM, Friddle C, Lanthorn TH, Zhang W (2009) Loss of the putative catalytic domain of HDAC4 leads to reduced thermal nociception and seizures while allowing normal bone development. PLoS ONE 4(8):e6612PubMedCrossRefGoogle Scholar
  180. Ravn K, Nielsen JB, Uldall P, Hansen FJ, Schwartz M (2003) No correlation between phenotype and genotype in boys with a truncating MECP2 mutation. J Med Genet 40(1):e5PubMedCrossRefGoogle Scholar
  181. 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(12):3153–3163PubMedCrossRefGoogle Scholar
  182. Reardon W (2002) Genitopatellar syndrome: a recognizable phenotype. Am J Med Genet 111:313–315PubMedCrossRefGoogle Scholar
  183. Reik W (2007) Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447(7143):425–432PubMedCrossRefGoogle Scholar
  184. Reisman D, Glaros S, Thompson EA (2009) The SWI/SNF complex and cancer. Oncogene 28(14):1653–1668PubMedCrossRefGoogle Scholar
  185. Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O’Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M (2011) DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA 305:68–77PubMedCrossRefGoogle Scholar
  186. Roelfsema JH, White SJ, Ariyürek 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(4):572–580PubMedCrossRefGoogle Scholar
  187. Ruhl DD, Jin J, Cai Y, Swanson S, Florens L, Washburn MP, Conaway RC, Conaway JW, Chrivia JC (2006) Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes. Biochemistry 45:5671–5677PubMedCrossRefGoogle Scholar
  188. Samaco RC, Nagarajan RP, Braunschweig D (2004) LaSalle JM (2004) Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders. Hum Mol Genet 13(6):629–639PubMedCrossRefGoogle Scholar
  189. Samaco RC, Hogart A, LaSalle JM (2005) Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet 14(4):483–492PubMedCrossRefGoogle Scholar
  190. Sanlaville D, Etchevers HC, Gonzales M, Martinovic J, Clément-Ziza M, Delezoide AL, Aubry MC, Pelet A, Chemouny S, Cruaud C, Audollent S, Esculpavit C, Goudefroye G, Ozilou C, Fredouille C, Joye N, Morichon-Delvallez N, Dumez Y, Weissenbach J, Munnich A, Amiel J, Encha-Razavi F, Lyonnet S, Vekemans M, Attié-Bitach T (2006) Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development. J Med Genet 43:211–217PubMedCrossRefGoogle Scholar
  191. Santen GW, Aten E, Sun Y, Almomani R, Gilissen C, Nielsen M, Kant SG, Snoeck IN, Peeters EA, Hilhorst-Hofstee Y, Wessels MW, den Hollander NS, Ruivenkamp CA, van Ommen GJ, Breuning MH, den Dunnen JT, van Haeringen A, Kriek M (2012) Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome. Nat Genet 44:379–380PubMedCrossRefGoogle Scholar
  192. Santos-Rebouças CB, Fintelman-Rodrigues N, Jensen LR, Kuss AW, Ribeiro MG, Campos M Jr, Santos JM, Pimentel MM (2011) A novel nonsense mutation in KDM5C/JARID1C gene causing intellectual disability, short stature and speech delay. Neurosci Lett 498:67–71PubMedCrossRefGoogle Scholar
  193. 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(4):590–601PubMedCrossRefGoogle Scholar
  194. Scuto A, Kirschbaum M, Kowolik C, Kretzner L, Juhasz A, Atadja P, Pullarkat V, Bhatia R, Forman S, Yen Y, Jove R (2008) The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells. Blood 111(10):5093–5100PubMedCrossRefGoogle Scholar
  195. Seenundun S, Rampalli S, Liu QC, Aziz A, Palii C, Hong S, Blais A, Brand M, Ge K, Dilworth FJ (2010) UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis. EMBO J 29(8):1401–1411PubMedCrossRefGoogle Scholar
  196. Seo S, Richardson GA, Kroll KL (2005) The SWI/SNF chromatin remodeling protein Brg1 is required for vertebrate neurogenesis and mediates transactivation of Ngn and NeuroD. Development 132(1):105–115PubMedCrossRefGoogle Scholar
  197. Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H (2002) Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35:243–254PubMedCrossRefGoogle Scholar
  198. Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N (2003) Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region. Biochem Biophys Res Commun 304:184–190PubMedCrossRefGoogle Scholar
  199. Siderius LE, Hamel BC, van Bokhoven H, de Jager F, van den Helm B, Kremer H, Heineman-de Boer JA, Ropers HH, Mariman EC (1999) X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3. Am J Med Genet 85:216–220PubMedCrossRefGoogle Scholar
  200. Simpson MA, Deshpande C, Dafou D, Vissers LE, Woollard WJ, Holder SE, Gillessen-Kaesbach G, Derks R, White SM, Cohen-Snuijf R, Kant SG, Hoefsloot LH, Reardon W, Brunner HG, Bongers EM, Trembath RC (2012) De novo mutations of the gene encoding the histone acetyltransferase KAT6B cause Genitopatellar syndrome. Am J Hum Genet 90(2):290–294PubMedCrossRefGoogle Scholar
  201. Slupianek A, Yerrum S, Safadi FF, Monroy MA (2010) The chromatin remodeling factor SRCAP modulates expression of prostate specific antigen and cellular proliferation in prostate cancer cells. J Cell Physiol 224(2):369–375PubMedCrossRefGoogle Scholar
  202. Song J, Teplova M, Ishibe-Murakami S, Patel DJ (2012) Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science 335(6069):709–712PubMedCrossRefGoogle Scholar
  203. Sopher BL, Ladd PD, Pineda VV, Libby RT, Sunkin SM, Hurley JB, Thienes CP, Gaasterland T, Filippova GN, La Spada AR (2011) CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA. Neuron 70:1071–1084PubMedCrossRefGoogle Scholar
  204. Stark KL, Xu B, Bagchi A, Lai WS, Liu H, Hsu R, Wan X, Pavlidis P, Mills AA, Karayiorgou M, Gogos JA (2008) Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat Genet 40:751–760PubMedCrossRefGoogle Scholar
  205. Tahiliani M, Mei P, Fang R, Leonor T, Rutenberg M, Shimizu F, Li J, Rao A, Shi Y (2007) The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature 447:601–605PubMedCrossRefGoogle Scholar
  206. Tao J, Hu K, Chang Q, Wu H, Sherman NE, Martinowich K, Klose RJ, Schanen C, Jaenisch R, Wang W, Sun YE (2009) Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function. Proc Natl Acad Sci USA 106(12):4882–4887PubMedCrossRefGoogle Scholar
  207. Tatton-Brown K, Rahman N (2007) Sotos syndrome. Eur J Hum Genet 15(3):264–271PubMedCrossRefGoogle Scholar
  208. Tatton-Brown K, Hanks S, Ruark E, Zachariou A, Duarte Sdel V, Ramsay E, Snape K, Murray A, Perdeaux ER, Seal S, Loveday C, Banka S, Clericuzio C, Flinter F, Magee A, McConnell V, Patton M, Raith W, Rankin J, Splitt M, Strenger V, Taylor C, Wheeler P, Temple KI, Cole T; Childhood Overgrowth Collaboration, Douglas J, Rahman N (2011) Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height. Oncotarget 2(12):1127-1133Google Scholar
  209. Thomas T, Voss AK, Chowdhury K, Gruss P (2000) Querkopf, a MYST family histone acetyltransferase, is required for normal cerebral cortex development. Development 127(12):2537–2548PubMedGoogle Scholar
  210. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, Jaenisch R, Sur M (2009) Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci USA106(6):2029-2034Google Scholar
  211. Tsai AC, Dossett CJ, Walton CS, Cramer AE, Eng PA, Nowakowska BA, Pursley AN, Stankiewicz P, Wiszniewska J, Cheung SW (2011) Exon deletions of the EP300 and CREBBP genes in two children with Rubinstein-Taybi syndrome detected by aCGH. Europ J Hum Genet 19:43–49PubMedCrossRefGoogle Scholar
  212. Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N (2012) Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet 44:376-378Google Scholar
  213. Urdinguio RG, Lopez-Serra L, Lopez-Nieva P, Alaminos M, Diaz-Uriarte R, Fernandez AF, Esteller M (2008) Mecp2-null mice provide new neuronal targets for Rett syndrome. PLoS ONE 3(11):e3669PubMedCrossRefGoogle Scholar
  214. Urdinguio RG, Sanchez-Mut JV, Esteller M (2009) Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol 8(11):1056–1072PubMedCrossRefGoogle Scholar
  215. Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC (2004) Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res 32(14):4100–4108PubMedCrossRefGoogle Scholar
  216. Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K, Lugtenberg D, Bienvenu T, Jensen LR, Gecz J, Moraine C, Marynen P, Fryns JP, Froyen G (2005) Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet 77(3):442–453PubMedCrossRefGoogle Scholar
  217. Van Houdt JK, Nowakowska BA, Sousa SB, van Schaik BD, Seuntjens E, Avonce N, Sifrim A, Abdul-Rahman OA, van den Boogaard MJ, Bottani A, Castori M, Cormier-Daire V, Deardorff MA, Filges I, Fryer A, Fryns JP, Gana S, Garavelli L, Gillessen-Kaesbach G, Hall BD, Horn D, Huylebroeck D, Klapecki J, Krajewska-Walasek M, Kuechler A, Lines MA, Maas S, Macdermot KD, McKee S, Magee A, de Man SA, Moreau Y, Morice-Picard F, Obersztyn E, Pilch J, Rosser E, Shannon N, Stolte-Dijkstra I, Van Dijck P, Vilain C, Vogels A, Wakeling E, Wieczorek D, Wilson L, Zuffardi O, van Kampen AH, Devriendt K, Hennekam R, Vermeesch JR (2012) Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nat Genet 44:445–449PubMedCrossRefGoogle Scholar
  218. Vecsey CG, Hawk JD, Lattal KM, Stein JM, Fabian SA, Attner MA, Cabrera SM, McDonough CB, Brindle PK, Abel T, Wood MA (2007) Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB: CBP-dependent transcriptional activation. J Neurosci 27:6128–6140PubMedCrossRefGoogle Scholar
  219. Villard L (2007) MECP2 mutations in males. J Med Genet 44:417–423PubMedCrossRefGoogle Scholar
  220. Viosca J, López-Ayala JP, Olivares R, Eckner R, Barco A (2010) Syndromic features and mild cognitive impairment in mice with genetic reduction on p300 activity: differential contribution of p300 and CBP to Rubinstein-Taybi syndrome etiology. Neurobiol Dis 37:186–194PubMedCrossRefGoogle Scholar
  221. Wang J, Weaver IC, Gauthier-Fisher A, Wang H, He L, Yeomans J, Wondisford F, Kaplan DR, Miller FD (2010) CBP histone acetyltransferase activity regulates embryonic neural differentiation in the normal and Rubinstein-Taybi syndrome brain. Dev Cell 18(1):114–125PubMedCrossRefGoogle Scholar
  222. Watson P, Black G, Ramsden S, Barrow M, Super M, Kerr B, Clayton-Smith J (2001) Angelman syndrome phenotype associated with mutations in MECP2, a gene encoding a methyl CpG binding protein. J Med Genet 38:224–228PubMedCrossRefGoogle Scholar
  223. Weaver DD, Graham CB, Thomas IT, Smith DW (1974) A new overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly. J Pediat 84:547–552PubMedCrossRefGoogle Scholar
  224. Wegorzewska I, Bell S, Cairns NJ, Miller TM, Baloh RH (2009) TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci USA 106(44):18809–18814PubMedCrossRefGoogle Scholar
  225. Willemsen MH, Vulto-van Silfhout AT, Nillesen WM, Wissink-Lindhout WM, van Bokhoven H, Philip N, Berry-Kravis EM, Kini U, van Ravenswaaij-Arts CM, Delle Chiaie B, Innes AM, Houge G, Kosonen T, Cremer K, Fannemel M, Stray-Pedersen A, Reardon W, Ignatius J, Lachlan K, Mircher C, Helderman van den Enden PT, Mastebroek M, Cohn-Hokke PE, Yntema HG, Drunat S, Kleefstra T (2012) Update on Kleefstra Syndrome. Mol Syndromol 2(3–5):202–212PubMedGoogle Scholar
  226. Williams SR, Aldred MA, Der Kaloustian VM, Halal F, Gowans G, McLeod DR, Zondag S, Toriello HV, Magenis RE, Elsea SH (2010) Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems. Am J Hum Genet 87:219–228PubMedCrossRefGoogle Scholar
  227. Winkelmann J, Lin L, Schormair B, Kornum BR, Faraco J, Plazzi G, Melberg A, Cornelio F, Urban AE, Pizza F, Poli F, Grubert F, Wieland T, Graf E, Hallmayer J, Strom TM, Mignot E (2012) Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum Mol Genet 21(10):2205–2210PubMedCrossRefGoogle Scholar
  228. Wolff D, Endele S, Azzarello-Burri S, Hoyer J, Zweier M, Schanze I, Schmitt B, Rauch A, Reis A, Zweier C (2012) In-frame deletion and missense mutations of the C-terminal helicase domain of SMARCA2 in three patients with Nicolaides-Baraitser syndrome. Molec Syndromol 2:237–244Google Scholar
  229. Wong MM, Cox L, Chrivia J (2007) The chromatin remodeling protein SRCAP is critical for deposition of the histone variant H2A.Z at promoters. J Biol Chem 282:26132–26139PubMedCrossRefGoogle Scholar
  230. Wong LH, McGhie JD, Sim M, Anderson MA, Ahn S, Hannan RD, George AJ, Morgan KA, Mann JR, Choo KH (2010) ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells. Genome Res 20(3):351–360PubMedCrossRefGoogle Scholar
  231. Wyngaarden LA, Delgado-Olguin P, Su IH, Bruneau BG, Hopyan S (2011) Ezh2 regulates anteroposterior axis specification and proximodistal axis elongation in the developing limb. Development 138(17):3759–3767PubMedCrossRefGoogle Scholar
  232. Xie W, Ling T, Zhou Y, Feng W, Zhu Q, Stunnenberg HG, Grummt I, Tao W (2012) The chromatin remodeling complex NuRD establishes the poised state of rRNA genes characterized by bivalent histone modifications and altered nucleosome positions. Proc Natl Acad Sci USA 109(21):8161–8166PubMedCrossRefGoogle Scholar
  233. Xu GL, Bestor TH, Bourc’his D, Hsieh CL, Tommerup N, Bugge M, Hulten M, Qu X, Russo JJ, Viegas-Péquignot E (1999) Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402:187–191PubMedCrossRefGoogle Scholar
  234. Xu J, Deng X, Disteche CM (2008) Sex-specific expression of the X-linked histone demethylase gene Jarid1c in brain. PLoS ONE 3(7):e2553PubMedCrossRefGoogle Scholar
  235. Yang X, Noushmehr H, Han H, Andreu-Vieyra C, Liang G, Jones PA (2012) Gene reactivation by 5-aza-2′-deoxycytidine-induced demethylation requires SRCAP-mediated H2A.Z insertion to establish nucleosome depleted regions. PLoS Genet 8(3):e1002604PubMedCrossRefGoogle Scholar
  236. Yasui DH, Peddada S, Bieda MC, Vallero RO, Hogart A, Nagarajan RP, Thatcher KN, Farnham PJ, Lasalle JM (2007) Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc Natl Acad Sci USA 104(49):19416–19421PubMedCrossRefGoogle Scholar
  237. Yazdani M, Deogracias R, Guy J, Poot RA, Bird A, Barde YA (2010) Disease modeling using embryonic stem cells: MeCP2 regulates nuclear size and RNA synthesis in neurons. Stem Cells 30(10):2128–2139CrossRefGoogle Scholar
  238. Yehezkel S, Segev Y, Viegas-Péquignot E, Skorecki K, Selig S (2008) Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions. Hum Mol Genet 17(18):2776–2789PubMedCrossRefGoogle Scholar
  239. Yoneda Y, Saitsu H, Touyama M, Makita Y, Miyamoto A, Hamada K, Kurotaki N, Tomita H, Nishiyama K, Tsurusaki Y, Doi H, Miyake N, Ogata K, Naritomi K, Matsumoto N (2012) Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features. J Hum Genet 57(3):207-211Google Scholar
  240. Yoo SY, Pennesi ME, Weeber EJ, Xu B, Atkinson R, Chen S, Armstrong DL, Wu SM, Sweatt JD, Zoghbi HY (2003) SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity. Neuron 37(3):383–401PubMedCrossRefGoogle Scholar
  241. 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 USA102(49):17551-17558Google Scholar
  242. Yu L, Wang Y, Huang S, Wang J, Deng Z, Zhang Q, Wu W, Zhang X, Liu Z, Gong W, Chen Z (2010) Structural insights into a novel histone demethylase PHF8. Cell Res 20(2):166–173PubMedCrossRefGoogle Scholar
  243. Yuan X, Feng W, Imhof A, Grummt I, Zhou Y (2007) Activation of RNA polymerase I transcription by cockayne syndrome group B protein and histone methyltransferase G9a. Mol Cell 27(4):585–595PubMedCrossRefGoogle Scholar
  244. Zachariah RM, Rastegar M (2012) Linking epigenetics to human disease and Rett syndrome: the emerging novel and challenging concepts in MeCP2 research. Neural Plast 2012:415825PubMedCrossRefGoogle Scholar
  245. Zhou Z, Hong EJ, Cohen S, Zhao WN, Ho HY, Schmidt L, Chen WG, Lin Y, Savner E, Griffith EC, Hu L, Steen JA, Weitz CJ, Greenberg ME (2006) Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron 52(2):255–269PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)BarcelonaSpain
  2. 2.Department of Physiological Sciences IISchool of Medicine, University of BarcelonaBarcelonaSpain
  3. 3.Institució Catalana de Recerca I Estudis Avançats (ICREA)BarcelonaSpain

Personalised recommendations