Epigenetics, Autism Spectrum, and Neurodevelopmental Disorders

Neurotherapeutics

Volumn 10, Issue 4, 2013, Pages 742-756

  Rangasamy, Sampathkumar ^a   D'Mello, Santosh R ^b   Narayanan, Vinodh ^a  

^a BARROW NEUROLOGICAL INSTITUTE   (United States)

^b UNIVERSITY OF TEXAS AT DALLAS   (United States)

Author keywords

Acetylation; Angelman; Autism; Fragile X; Histones; Methylation; Neurodevelopmental disorders; Prader Willi; Rett

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; BINDING PROTEIN; BRAIN DERIVED NEUROTROPHIC FACTOR; COMPLEMENTARY RNA; DNA TOPOISOMERASE INHIBITOR; ESTROGEN RECEPTOR; GYRASE INHIBITOR; HISTONE ACETYLTRANSFERASE; IRINOTECAN; TOPOTECAN; VALPROIC ACID;

ALLELE; AUTISM; BRAIN REGION; CELL DIVISION; CELL MATURATION; CENTRAL NERVOUS SYSTEM DISEASE; CHROMATIN ASSEMBLY AND DISASSEMBLY; CHROMATIN STRUCTURE; DISEASE SEVERITY; DNA METHYLATION; DNA MODIFICATION; DNA SEQUENCE; DOWN SYNDROME; EPIGENETICS; EPILEPSY; FRAGILE X SYNDROME; FRAMESHIFT MUTATION; GENE DISRUPTION; GENE DUPLICATION; GENE EXPRESSION REGULATION; GENE REPRESSION; GENE SILENCING; GENETIC LINKAGE; GENETIC MARKER; GENETIC TRANSCRIPTION; GENOME IMPRINTING; HAPPY PUPPET SYNDROME; HISTONE MODIFICATION; HUMAN; HYPERPHAGIA; HYPOGONADISM; KABUKI MAKEUP SYNDROME; MECP2 DUPLICATION SYNDROME; MENTAL RETARDATION MALFORMATION SYNDROME; NERVE CELL; NERVE CELL GROWTH; NEURODEVELOPMENTAL DISORDER; NEUROPATHOLOGY; NONHUMAN; OBESITY; PRADER WILLI SYNDROME; PREVALENCE; PRIORITY JOURNAL; PROMOTER REGION; REGULATORY MECHANISM; RETT SYNDROME; REVIEW; SINGLE CELL ANALYSIS; TRANSCRIPTION ELONGATION;

ABNORMALITIES, MULTIPLE; ANGELMAN SYNDROME; CHILD; CHILD DEVELOPMENT DISORDERS, PERVASIVE; DNA METHYLATION; EPIGENESIS, GENETIC; FACE; FRAGILE X SYNDROME; HEMATOLOGIC DISEASES; HISTONES; HUMANS; PRADER-WILLI SYNDROME; RETT SYNDROME; VESTIBULAR DISEASES;

EID: 84886241144     PISSN: 19337213     EISSN: 18787479     Source Type: Journal    
DOI: 10.1007/s13311-013-0227-0     Document Type: Review

References (158)

1. Kanner L. Autistic disturbances of affective contact. Nervous Child 1943;2: 217-250.
2. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders-Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ 2012;30: 61: 1-19.
3. Brugha TS, McManus S, Bankart J, et al. Epidemiology of autism spectrum disorders in adults in the community in England. Arch Gen Psychiatry 2011;68: 459-465.
4. Geschwind DH, Levitt P. Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol 2007;17: 103-111.
5. Dietert RR, Dietert JM, Dewitt JC. Environmental risk factors for autism. Emerg Health Threats J 2011;4: 10. 3402.
6. Sebat J, Lakshmi B, Malhotra D, et al. Strong association of de novo copy number mutations with autism. Science 2007;316: 445-449.
7. Folstein S, Rutter M. Genetic influences and infantile autism. Nature 1977;265: 726-728.
8. Folstein S, Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977;18: 297-321.
9. Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 1989;30: 405-416.
10. Wahlström J, Steffenburg S, Hellgren L, Gillberg C. Chromosome findings in twins with early-onset autistic disorder. Am J Med Genet 1989;32: 19-21.
11. Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;25: 63-77.
12. Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011;68: 1095-1102.
13. Waddington CH. The epigenotype. Endeavour 1942;1: 18-20.
14. Fagiolini M, Jensen CL, Champagne FA. Epigenetic influences on brain development and plasticity. Curr Opin Neurobiol 2009;19: 207-212.
15. IACC/OARC Autism Spectrum Disorder Research Publications Analysis Report. The Global Landscape of Autism Research. July 2012 Office of Autism Research Coordination (OARC), National Institute of Mental Health and Thomson Reuters, Inc. on behalf of the Interagency Autism Coordinating Committee (IACC).
16. Crouse HV. The controlling element in sex chromosome behavior in sciara. Genetics 1960;45: 1429-1443.
17. Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293: 1089-93.
18. Sha K. A mechanistic view of genomic imprinting. Annu Rev Genomics Hum Genet 2008;9: 197-216.
19. Morey C, Avner P. Genetics and epigenetics of the X chromosome. Ann N Y Acad Sci 2010;1214: E18-E33.
20. Ferguson-Smith AC. Genomic imprinting: the emergence of an epigenetic paradigm. Nat Rev Genet 2011;12: 565-575.
21. Reik W, Walter J. Genomic imprinting: parental influence on the genome. Nat Rev Genet 2001;2: 21-32.
22. Abramowitz LK, Bartolomei MS. Genomic imprinting: recognition and marking of imprinted loci. Curr Opin Genet Dev 2012;22: 72-78.
23. Gregg C, Zhang J, Weissbourd B, Luo S, Schroth GP, Haig D, Dulac C. High resolution analysis of parent-of-origin allelic expression in the mouse brain. Science. 2010;329: 643-648.
24. Butler MG. Genomic imprinting disorders in humans: a mini-review. J Assist Reprod Genet 2009;26: 477-486.
25. Keverne B. Monoallelic gene expression and mammalian evolution. Bioessays 2009;31: 1318-1326.
26. Tollkuhn J, Xu X, Shah NM. A custody battle for the mind: evidence for extensive imprinting in the brain. Neuron 2010;67: 359-362.
27. Buiting K. Prader-Willi syndrome and Angelman syndrome. Am J Med Genet Part C Semin Med Genet 2010;153C: 365-376.
28. Nicholls RD, Knepper JL. Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes. Annu Rev Genomics Hum Genet 2001;2: 153-175.
29. van Buggenhout G, Fryns JP. Angelman syndrome (AS, MIM 105830). Eur J Hum Genet 2009;17: 1367-1373.
30. Lalande M, Calciano MA. Molecular epigenetics of Angelman syndrome. Cell Mol Life Sci 2007;64: 947-960.
31. Mabb AM, Judson MC, Zylka MJ, Philpot BD. Angelman syndrome: insights into genomic imprinting and neurodevelopmental phenotypes. Trends Neurosci 2011;34: 293-303.
32. Lee JT, Bartolomei MS. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 2013;152: 1308-1323.
33. Dindot SV, Antalffy BA, Bhattacharjee MB, Beaudet AL. The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum Mol Genet 2008;17: 111-118.
34. Verona RI, Mann MR, Bartolomei MS. Genomic imprinting: intricacies of epigenetic regulation in clusters. Annu Rev Cell Dev Biol 2003;19: 237-259.
35. Rougeulle C, Cardoso C, Fontés M, Colleaux L, Lalande M. An imprinted antisense RNA overlaps UBE3A and a second maternally expressed transcript. Nat Genet 1998;19: 15-16.
36. Yamasaki K, Joh K, Ohta T, et al. Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Hum Mol Genet 2003;12: 837-847.
37. Chamberlain SJ, Brannan CI. The Prader-Willi syndrome imprinting center activates the paternally expressed murine Ube3a antisense transcript but represses paternal Ube3a. Genomics 2001;73: 316-322.
38. Meng L, Person RE, Beaudet AL. Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a. Hum Mol Genet 2012;21: 3001-3012.
39. Chamberlain SJ, Chen PF, Ng KY, et al. Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes. Proc Natl Acad Sci U S A 2010;107: 17668-17673.
40. Huang HS, Allen JA, Mabb AM, et al. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 2011;481: 185-189.
41. Lee PD. Disease management of Prader-Willi syndrome. Expert Opin Pharmacother 2002;3: 1451-1459.
42. Horsthemke B, Wagstaff J. Mechanisms of imprinting of the Prader-Willi/Angelman region. Am J Med Genet A 2008;146A: 2041-2052.
43. Bittel DC, Butler MG. Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med 2005;7: 1-20.
44. Duker AL, Ballif BC, Bawle EV et al. Paternally inherited microdeletion at 15q11. 2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader-Willi syndrome. Eur J Hum Genet 2010;18: 1196-1201.
45. Berdasco M, Esteller M. Genetic syndromes caused by mutations in epigenetic genes. Hum Genet 2013;132: 359-383.
46. Schroer RJ, Phelan MC, Michaelis RC, et al. Autism and maternally derived aberrations of chromosome 15q. Am J Med Genet 1998;76: 327.
47. Wang NJ, Liu D, Parokonny AS, Schanen NC. High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage. Am J Hum Genet 2004;75: 267-281.
48. Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008;9: 341-355.
49. Schanen NC. Epigenetics of autism spectrum disorders. Hum Mol Genet 2006;15: R138-R150.
50. Hogart A, Leung KN, Wang NJ, et al. Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. J Med Genet 2009;46: 86-93.
51. Smith SE, Zhou YD, Zhang G, Jin Z, Stoppel DC, Anderson MP. Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice. Sci Transl Med 2011;3: 103ra97.
52. Cook EH Jr, Lindgren V, Leventhal BL, et al. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 1997;60: 928-934.
53. Bolton PF, Dennis NR, Browne CE, et al. The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders. Am J Med Genet 2001;105: 675-685.
54. Di Rocco A, Loggini A, Di Rocco M, et al. Paradoxical worsening of seizure activity with pregabalin in an adult with isodicentric 15 (IDIC-15) syndrome involving duplications of the GABRB3, GABRA5 and GABRG3 genes. BMC Neurol 2013;13: 43.
55. Hogart A, Nagarajan RP, Patzel KA, Yasui DH, Lasalle JM. 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum Mol Genet 2007;16: 691-703.
56. Cummings CJ, Zoghbi HY. Trinucleotide repeats: mechanisms and pathophysiology. Annu Rev Genomics Hum Genet 2000;1: 281-328.
57. Coffee B, Keith K, Albizua I, et al. Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet 2009;85: 503-514.
58. Santoro MR, Bray SM, Warren ST. Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol 2012;7: 219-245.
59. Baker JK, Seltzer MM, Greenberg JS. Behaviour problems, maternal internalising symptoms and family relations in families of adolescents and adults with fragile X syndrome. J Intellect Disabil Res 2012;56: 984-995.
60. Verkerk AJ, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991;65: 905-914.
61. Bhakar AL, Dölen G, Bear MF. The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci 2012;35: 417-443.
62. Heitz D, Rousseau F, Devys D, et al. Isolation of sequences that span the fragile-X and identification of a fragile X-related CpG island. Science 1991;251: 1236-1239.
63. Hirst MC, White PJ. Cloned human FMR1 trinucleotide repeats exhibit a length-and orientation-dependent instability suggestive of in vivo lagging strand secondary structure. Nucleic Acids Res 1998;26: 2353-2358.
64. Pietrobono R, Tabolacci E, Zalfa F, et al. Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum Mol Genet 2005;14: 267-277.
65. Tabolacci E, Pietrobono R, Moscato U, Oostra BA, Chiurazzi P, Neri G. Differential epigenetic modifications in the FMR1 gene of the fragile X syndrome after reactivating pharmacological treatments. Eur J Hum Genet 2005;13: 641-648.
66. Sheridan SD, Theriault KM, Reis SA, et al. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS One 2011;6: e26203.
67. Jacquemont S, Hagerman RJ, Leehey MA, et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 2004;291: 460-469.
68. Hagerman RJ, Leavitt BR, Farzin F, et al. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet 2004;74: 1051-1056.
69. Penagarikano O, Mulle JG, Warren ST. The pathophysiology of fragile x syndrome. Annu Rev Genomics Hum Genet 2007;8: 109-129.
70. Alisch RS, Wang T, Chopra P, Visootsak J, Conneely KN, Warren ST. Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus. BMC Med Genet 2013;14: 18.
71. Urbach A, Bar-Nur O, Daley GQ, Benvenisty N. Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 2010;6: 407-411.
72. Handa V, Saha T, Usdin K. The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer. Nucleic Acids Res 2003;31: 6243-6248.
73. Verdel A, Jia S, Gerber S, et al. RNAi-mediated targeting of heterochromatin by the RITS complex. Science 2004;303: 672-676.
74. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001;293: 1068-1070.
75. Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 2008;9: 465-476.
76. Hashimshony T, Zhang J, Keshet I, Bustin M, Cedar H. The role of DNA methylation in setting up chromatin structure during development. Nat Genet 2003;34: 187-192.
77. Lorincz MC, Dickerson DR, Schmitt M, Groudine M. Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat Struct Mol Biol 2004;11: 1068-1075.
78. Hendrich B, Bird A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 1998;18: 6538-6547.
79. Fraga MF, Ballestar E, Montoya G, Taysavang P, Wade PA, Esteller M. The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties. Nucleic Acids Res 2003;31: 1765-1774.
80. Rauch C, Trieb M, Wibowo FR, Wellenzohn B, Mayer E, Liedl KR. Towards an understanding of DNA recognition by the methyl-CpG binding domain 1. J Biomol Struct Dyn 2005;22: 695-706.
81. Hendrich B, Tweedie S. The methyl-CpG binding domain and the evolving role of DNA methylation in animals. Trends Genet 2003;19: 269-277.
82. Roloff TC, Ropers HH, Nuber UA. Comparative study of methyl-CpG-binding domain proteins. BMC Genomics 2003;4: 1.
83. Fournier A, Sasai N, Nakao M, Defossez PA. The role of methyl-binding proteins in chromatin organization and epigenome maintenance. Brief Funct Genomics 2012;11: 251-264.
84. Wan M, Lee SS, Zhang X, et al. Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet 1999;65: 1520-1529.
85. Moretti P, Zoghbi HY. MeCP2 dysfunction in Rett syndrome and related disorders. Curr Opin Genet Dev 2006;16: 276-281.
86. Gonzales ML, LaSalle JM. The role of MeCP2 in brain development and neurodevelopmental disorders. Curr Psychiatry Rep 2010;12: 127-134.
87. Amir RE, van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999;23: 185-188.
88. Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol 1983;14: 471-479.
89. Dunn HG. Neurons and neuronal systems involved in the pathophysiologies of Rett syndrome. Brain Dev 2001;23(Suppl. 1): S99-S100.
90. Dunn HG, MacLeod PM. Rett syndrome: review of biological abnormalities. Can J Neurol Sci 2001;28: 16-29.
91. Bauman ML, Kemper TL, Arin DM. Pervasive neuroanatomic abnormalities of the brain in three cases of Rett's syndrome. Neurology 1995;45: 1581-1586.
92. Bauman ML, Kemper TL, Arin DM. Microscopic observations of the brain in Rett syndrome. Neuropediatrics 1995;26: 105-108.
93. Belichenko PV, Oldfors A, Hagberg B, Dahlström A. Rett syndrome: 3-D confocal microscopy of cortical pyramidal dendrites and afferents. Neuroreport 1994;5: 1509-1513.
94. Jentarra GM, Olfers SL, Rice SG, et al. Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation. BMC Neurosci 2010;11: 19.
95. Armstrong DD. Neuropathology of Rett syndrome. J Child Neurol 2005;20: 747-753.
96. Guy J, Cheval H, Selfridge J, Bird A. The role of MeCP2 in the brain. Annu Rev Cell Dev Biol 2011;27: 631-652.
97. Nan X, Ng HH, Johnson CA, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 1998;393: 386-389.
98. Baker SA, Chen L, Wilkins AD, Yu P, Lichtarge O, Zoghbi HY. An AT-hook domain in MeCP2 determines the clinical course of Rett syndrome and related disorders. Cell 2013;152: 984-996.
99. Hite KC, Adams VH, Hansen JC. Recent advances in MeCP2 structure and function. Biochem Cell Biol 2009;87: 219-227.
100. van Esch H. MECP2 duplication syndrome. Mol Syndromol 2012;2: 128-136.
101. Peters SU, Hundley RJ, Wilson AK, Carvalho CM, Lupski JR, Ramocki MB. Brief report: regression timing and associated features in MECP2 duplication syndrome. J Autism Dev Disord 2013;43: 2484-2490.
102. Ramocki MB, Tavyev YJ, Peters SU. The MECP2 duplication syndrome. Am J Med Genet A 2010;152A: 1079-1088.
103. Himada S, Okamoto N, Ito et al. MECP2 duplication syndrome in both genders. Brain Dev 2013;35: 411-419.
104. Lugtenberg D, Kleefstra T, Oudakker AR, et al. Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy. Eur J Hum. Genet 2009;17: 444-453.
105. van Esch H, Bauters M, Ignatius J, et al. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet 2005;77: 442-453.
106. Luikenhuis S, Giacometti E, Beard CF, Jaenisch R. Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci U S A 2004;101: 6033-6038.
107. Collins AL, Levenson JM, Vilaythong AP, et al. Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 2004;13: 2679-2689.
108. Yasui DH, Peddada S, Bieda MC, et al. Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc Natl Acad Sci U S A 2007;104: 19416-19421.
109. Singh J, Saxena A, Christodoulou J, Ravine D. MECP2 genomic structure and function: insights from ENCODE. Nucleic Acids Res 2008;36: 6035-6047.
110. Meehan RR, Lewis JD, Bird AP. Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucleic Acids Res 1992;20: 5085-5092.
111. Lewis JD, Meehan RR, Henzel WJ, et al. Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 1992;69: 905-914.
112. Jones PL, Veenstra GJ, Wade PA, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 1998;19: 187-191.
113. Chahrour M, Jung SY, Shaw C, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008;320: 1224-1229.
114. Mnatzakanian GN, Lohi H, Munteanu I, et al. A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome. Nat Genet 2004;36: 339-341.
115. Dragich JM, Kim YH, Arnold AP, Schanen NC. Differential distribution of the MeCP2 splice variants in the postnatal mouse brain. J Comp Neurol 2007;501: 526-542.
116. Dastidar SG, Bardai FH, Ma C, et al. Isoform-specific toxicity of Mecp2 in postmitotic neurons: suppression of neurotoxicity by FoxG1. J Neurosci 2012;32: 2846-2855.
117. Zhou Z, Hong EJ, Cohen S, et al. Brain-specific phosphorylation of MeCP2 regulates activity-dependent BDNF transcription, dendritic growth, and spine maturation. Neuron 2006;52: 255-269.
118. Chen WG, Chang Q, Lin Y, et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 2003;302: 885-889.
119. Zocchi L, Sassone-Corsi P. SIRT1-mediated deacetylation of MeCP2 contributes to BDNF expression. Epigenetics 2012;7: 695-700.
120. Horike S, Cai S, Miyano M, Cheng JF, Kohwi-Shigematsu T. Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat Genet 2005;37: 31-40.
121. Yasui DH, Xu H, Dunaway KW, Lasalle JM, Jin LW, Maezawa I. MeCP2 modulates gene expression pathways in astrocytes. Mol Autism 2013;4: 3.
122. Abuhatzira L, Shamir A, Schones DE, Schäffer AA, Bustin M. The chromatin-binding protein HMGN1 regulates the expression of methyl CpG-binding protein 2 (MECP2) and affects the behavior of mice. J Biol Chem 2011;D286: 42051-42062.
123. Mellén M, Ayata P, Dewell S, Kriaucionis S, Heintz N. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 2012;151: 1417-1430.
124. Nagarajan RP, Patzel KA, Martin M, et al. MECP2 promoter methylation and X chromosome inactivation in autism. Autism Res 2008;1: 169-178.
125. Nagarajan RP, Hogart AR, Gwye Y, Martin MR, LaSalle JM. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics 2006;1: e1-11.
126. Grafodatskaya D, Chung B, Szatmari P, Weksberg R. Autism spectrum disorders and epigenetics. J Am Acad Child Adolesc Psychiatry 2010;49: 794-809.
127. Allan AM, Liang X, Luo Y, et al. The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits. Hum Mol Genet 2008;17: 2047-2057.
128. Cukier HN, Rabionet R, Konidari I, et al. Novel variants identified in methyl-CpG-binding domain genes in autistic individuals. Neurogenetics 2010;11: 291-303.
129. Cukier HN, Lee JM, Ma D, et al. The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1. Autism Res 2012;5: 385-397.
130. Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. J Pediatr 1981;99: 570-573.
131. Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr 1981;99: 565-569.
132. Ng SB, Bigham AW, Buckingham KJ, et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet 2010;42: 790-793.
133. Bokinni Y. Kabuki syndrome revisited. J Hum Genet 2012;57: 223-227.
134. Micale L, Augello B, Fusco C, et al. Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients. Orphanet J Rare Dis 2011;6: 38.
135. Priolo M, Micale L, Augello B, et al. Absence of deletion and duplication of MLL2 and KDM6A genes in a large cohort of patients with Kabuki syndrome. Mol Genet Metab 2012;107: 627-629.
136. Banka S, Veeramachaneni R, Reardon W, et al. How genetically heterogeneous is Kabuki syndrome: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum. Eur J Hum Genet 2012;20: 381-388.
137. Lederer D, Grisart B, Digilio MC, et al. Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. Am J Hum Genet 2012;90: 119-124.
138. Greenfield A, Carrel L, Pennisi D, et al. The UTX gene escapes X inactivation in mice and humans. Hum Mol Genet 1998;7: 737-742.
139. Prasad R, Zhadanov AB, Sedkov Y, et al. Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax. Oncogene 1997;15: 549-560.
140. Shilatifard A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol 2008;20: 341-348.
141. Shi Y, Whetstine JR. Dynamic regulation of histone lysine methylation by demethylases. Mol Cell 2007;25: 1-14.
142. Issaeva I, Zonis Y, Rozovskaia T, et al. Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth. Mol Cell Biol 2007;27: 1889-1903.
143. Vicent GP, Nacht AS, Font-Mateu J, et al. Four enzymes cooperate to displace histone H1 during the first minute of hormonal gene activation. Genes Dev 2011;25: 845-862.
144. Guo C, Chang CC, Wortham M, et al. Global identification of MLL2-targeted loci reveals MLL2's role in diverse signaling pathways. Proc Natl Acad Sci U S A 2012;109: 17603-17608.
145. Dhar SS, Lee SH, Kan PY, et al. Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4. Genes Dev 2012; 26: 2749-2762.
146. Kerimoglu C, Agis-Balboa RC, Kranz A, et al. Histone-methyltransferase MLL2 (KMT2B) is required for memory formation in mice. J Neurosci 2013;33: 3452-3464.
147. Saitoh S, Wada T. Parent-of-origin specific histone acetylation and reactivation of a key imprinted gene locus in Prader-Willi syndrome. Am J Hum Genet 2000;66: 1958-1962.
148. Garg SK, Lioy DT, Cheval H, et al. Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome. J Neurosci 2013;33: 13612-13620.
149. Derecki NC, Cronk JC, Lu Z, et al. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 2012;484: 105-109.
150. Martinowich K, Hattori D, Wu H, et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 2003;302: 890-893.
151. Chang Q, Khare G, Dani V, Nelson S, Jaenisch R. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 2006;49: 341-348.
152. Ogier M, Wang H, Hong E, Wang Q, Greenberg ME, Katz DM. Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J Neurosci 2007;27: 10912-10917.
153. Itoh M, Ide S, Takashima S, et al. Methyl CpG-binding protein 2 (a mutation of which causes Rett syndrome) directly regulates insulin-like growth factor binding protein 3 in mouse and human brains. J Neuropathol Exp Neurol 2007;66: 117-123.
154. Tropea D, Giacometti E, Wilson NR, et al. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A 2009;106: 2029-2034.
155. Todd PK, Oh SY, Krans A, et al. Histone deacetylases suppress CGG repeat-induced neurodegeneration via transcriptional silencing in models of fragile X tremor ataxia syndrome. PLoS Genet 2010;6: e1001240.
156. Torrioli M, Vernacotola S, Setini C, et al. Treatment with valproic acid ameliorates ADHD symptoms in fragile X syndrome boys. Am J Med Genet A 2010;152A: 1420-1427.
157. Jiang J, Jing Y, Cost GJ, et al. Translating dosage compensation to trisomy 21. Nature 2013;500: 296-300.
158. Gross C, Berry-Kravis EM, Bassell GJ. Therapeutic strategies in fragile X syndrome: dysregulated mGluR signaling and beyond. Neuropsychopharmacology 2012;37: 178-195.