Epigenetic regulators sculpt the plastic brain

Frontiers in Biology - Tập 12 - Trang 317-332 - 2017
Ji-Song Guan1, Hong Xie2, San-Xiong Liu2
1ShanghaiTech University, Shanghai, China
2School of Life Sciences, Tsinghua University, Beijing, China

Tóm tắt

Epigenetic regulation is a level of transcriptional regulation that occurs in addition to the genetic programming found in biological systems. In the brain, the epigenetic machinery gives the system an opportunity to adapt to a given environment to help not only the individual but also the species survive and expand. However, such a regulatory system has risks, as mutations resulting from epigenetic regulation can cause severe neurological or psychiatric disorders. Here, we review the most recent findings regarding the epigenetic mechanisms that control the activitydependent gene transcription leading to synaptic plasticity and brain function and the defects in these mechanisms that lead to neurological disorders. A search was carried out systematically, searching all relevant publications up to June 2017, using the PubMed search engine. The following keywords were used: “activity induced epigenetic,” “gene transcription,” and “neurological disorders.” Awide range of studies focused on the roles of epigenetics in transgenerational inheritance, neural differentiation, neural circuit assembly and brain diseases. Thirty-one articles focused specifically on activity-induced epigenetic modifications that regulated gene transcription and memory formation and consolidation. Activity-dependent epigenetic mechanisms of gene expression regulation contribute to basic neuronal physiology, and defects were associated with an elevated risk for brain disorders.

Tài liệu tham khảo

Devor A, Andreassen O A, Wang Y, Mäki-Marttunen T, Smeland O B, Fan C C, Schork A J, Holland D, Thompson W K, Witoelar A, Chen C H, Desikan R S, McEvoy L K, Djurovic S, Greengard P, Svenningsson P, Einevoll G T, Dale A M (2017). Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia. Mol Psychiatry, 22(6): 792–801 De Rubeis S, He X, Goldberg A P, Poultney C S, Samocha K, Cicek A E, Kou Y, Liu L, Fromer M, Walker S, Singh T, Klei L, Kosmicki J, Shih-Chen F, Aleksic B, Biscaldi M, Bolton P F, Brownfeld J M, Cai J, Campbell N G, Carracedo A, Chahrour M H, Chiocchetti A G, Coon H, Crawford E L, Curran S R, Dawson G, Duketis E, Fernandez B A, Gallagher L, Geller E, Guter S J, Hill R S, Ionita-Laza J, Jimenz Gonzalez P, Kilpinen H, Klauck S M, Kolevzon A, Lee I, Lei I, Lei J, Lehtimäki T, Lin C F, Ma’ayan A, Marshall C R, McInnes A L, Neale B, Owen M J, Ozaki N, Parellada M, Parr J R, Purcell S, Puura K, Rajagopalan D, Rehnström K, Reichenberg A, Sabo A, Sachse M, Sanders S J, Schafer C, Schulte-Rüther M, Skuse D, Stevens C, Szatmari P, Tammimies K, Valladares O, Voran A, Li-San W, Weiss L A, Willsey A J, Yu T W, Yuen R K, Cook E H, Freitag C M, Gill M, Hultman C M, Lehner T, Palotie A, Schellenberg G D, Sklar P, State M W, Sutcliffe J S, Walsh C A, Scherer SW, ZwickME, Barett J C, Cutler D J, Roeder K, Devlin B, Daly M J, Buxbaum J D, and the DDD Study, and the Homozygosity Mapping Collaborative for Autism, and the UK10K Consortium (2014). Synaptic, transcriptional and chromatin genes disrupted in autism. Nature, 515(7526): 209–215 Stessman H A, Xiong B, Coe B P, Wang T, Hoekzema K, Fenckova M, Kvarnung M, Gerdts J, Trinh S, Cosemans N, Vives L, Lin J, Turner T N, Santen G, Ruivenkamp C, Kriek M, van Haeringen A, Aten E, Friend K, Liebelt J, Barnett C, Haan E, Shaw M, Gecz J, Anderlid B M, Nordgren A, Lindstrand A, Schwartz C, Kooy R F, Vandeweyer G, Helsmoortel C, Romano C, Alberti A, Vinci M, Avola E, Giusto S, Courchesne E, Pramparo T, Pierce K, Nalabolu S, Amaral D G, Scheffer I E, Delatycki M B, Lockhart P J, Hormozdiari F, Harich B, Castells-Nobau A, Xia K, Peeters H, Nordenskjöld M, Schenck A, Bernier R A, Eichler E E (2017). Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and develop-mental-disability biases. Nat Genet, 49(4): 515–526 Guan J S, Haggarty S J, Giacometti E, Dannenberg J H, Joseph N, Gao J, Nieland T J, Zhou Y, Wang X, Mazitschek R, Bradner J E, DePinho R A, Jaenisch R, Tsai L H (2009). HDAC2 negatively regulates memory formation and synaptic plasticity. Nature, 459(7243): 55–60 Gräff J, Rei D, Guan J S, Wang W Y, Seo J, Hennig K M, Nieland T J, Fass DM, Kao P F, Kahn M, Su S C, Samiei A, Joseph N, Haggarty S J, Delalle I, Tsai L H (2012). An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature, 483(7388): 222–226 Waddington C H (2012). The epigenotype. 1942. Int J Epidemiol, 41(1): 10–13 Bird A (2007). Perceptions of epigenetics. Nature, 447(7143): 396–398 Bird A (2002). DNA methylation patterns and epigenetic memory. Genes Dev, 16(1): 6–21 Laird P W (2003). The power and the promise of DNA methylation markers. Nat Rev Cancer, 3(4): 253–266 Ramsahoye B H, Biniszkiewicz D, Lyko F, Clark V, Bird A P, Jaenisch R (2000). Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase3a. Proc Natl Acad Sci USA, 97(10): 5237–5242 Matzke M A, Birchler J A (2005). RNAi-mediated pathways in the nucleus. Nat Rev Genet, 6(1): 24–35 Jenuwein T, Allis C D (2001). Translating the histone code. Science, 293 (5532): 1074–1080 Kouzarides T (2007). Chromatin modifications and their function. Cell, 128(4): 693–705 Pusarla R H, Bhargava P (2005). Histones in functional diversification. Core histone variants. FEBS J, 272(20): 5149–5168 Talbert P B, Henikoff S (2010). Histone variants–ancient wrap artists of the epigenome. Nat Rev Mol Cell Biol, 11(4): 264–275 Becker P B, Hörz W (2002). ATP-dependent nucleosome remodeling. Annu Rev Biochem, 71(1): 247–273 Clapier C R, Cairns B R (2009). The biology of chromatin remodeling complexes. Annu Rev Biochem, 78(1): 273–304 Borrelli E, Nestler E J, Allis C D, Sassone-Corsi P (2008). Decoding the epigenetic language of neuronal plasticity. Neuron, 60(6): 961–974 Roth T L, Sweatt J D (2009). Regulation of chromatin structure in memory formation. Curr Opin Neurobiol, 19(3): 336–342 Sweatt J D (2016). GENE EXPRESSION. Chromatin controls behavior. Science, 353(6296): 218–219 Zovkic I B, Sweatt J D (2015). Memory-Associated Dynamic Regulation of the “Stable” Core of the Chromatin Particle. Neuron, 87(1): 1–4 Sweatt J D (2013). The emerging field of neuroepigenetics. Neuron, 80 (3): 624–632 Kim T K, Hemberg M, Gray J M, Costa A M, Bear D M, Wu J, Harmin D A, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley P F, Kreiman G, Greenberg M E (2010). Widespread transcription at neuronal activity-regulated enhancers. Nature, 465(7295): 182–187 Sui L, Wang Y, Ju L H, Chen M (2012). Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in long-term potentiation in rat medial prefrontal cortex. Neurobiol Learn Mem, 97(4): 425–440 Malik A N, Vierbuchen T, Hemberg M, Rubin A A, Ling E, Couch C H, Stroud H, Spiegel I, Farh K K, Harmin D A, Greenberg M E (2014). Genome-wide identification and characterization of functional neuronal activity-dependent enhancers. Nat Neurosci, 17(10): 1330–1339 Gräff J, Woldemichael B T, Berchtold D, Dewarrat G, Mansuy I M (2012). Dynamic histone marks in the hippocampus and cortex facilitate memory consolidation. Nat Commun, 3: 991 Naruse Y, Oh-hashi K, Iijima N, Naruse M, Yoshioka H, Tanaka M (2004). Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation. Mol Cell Biol, 24 (14): 6278–6287 Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun Y E (2003). DNA methylation-related chromatin remodeling in activitydependent BDNF gene regulation. Science, 302(5646): 890–893 Guo J U, Ma D K, Mo H, Ball MP, Jang MH, Bonaguidi MA, Balazer J A, Eaves H L, Xie B, Ford E, Zhang K, Ming G L, Gao Y, Song H (2011). Neuronal activity modifies the DNA methylation landscape in the adult brain. Nat Neurosci, 14(10): 1345–1351 Crosio C, Heitz E, Allis C D, Borrelli E, Sassone-Corsi P (2003). Chromatin remodeling and neuronal response: multiple signaling pathways induce specific histone H3 modifications and early gene expression in hippocampal neurons. J Cell Sci, 116(Pt 24): 4905–4914 Levenson J M, O’Riordan K J, Brown K D, Trinh M A, Molfese D L, Sweatt J D (2004). Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem, 279(39): 40545–40559 Crosio C, Cermakian N, Allis C D, Sassone-Corsi P (2000). Light induces chromatin modification in cells of the mammalian circadian clock. Nat Neurosci, 3(12): 1241–1247 Dyrvig M, Hansen H H, Christiansen S H, Woldbye D P, Mikkelsen J D, Lichota J (2012). Epigenetic regulation of Arc and c-Fos in the hippocampus after acute electroconvulsive stimulation in the rat. Brain Res Bull, 88(5): 507–513 Gupta S, Kim S Y, Artis S, Molfese D L, Schumacher A, Sweatt J D, Paylor R E, Lubin F D (2010). Histone methylation regulates memory formation. J Neurosci, 30(10): 3589–3599 Gupta-Agarwal S, Franklin A V, Deramus T, Wheelock M, Davis R L, McMahon L L, Lubin F D (2012). G9a/GLP histone lysine dimethyltransferase complex activity in the hippocampus and the entorhinal cortex is required for gene activation and silencing during memory consolidation. J Neurosci, 32(16): 5440–5453 Chwang W B, O’Riordan K J, Levenson J M, Sweatt J D (2006). ERK/ MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning. Learn Mem, 13(3): 322–328 Miller C A, Sweatt J D (2007). Covalent modification of DNA regulates memory formation. Neuron, 53(6): 857–869 Lubin F D, Roth T L, Sweatt J D (2008). Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci, 28 (42): 10576–10586 Miller C A, Gavin C F, White J A, Parrish R R, Honasoge A, Yancey C R, Rivera IM, Rubio MD, Rumbaugh G, Sweatt J D (2010). Cortical DNA methylation maintains remote memory. Nat Neurosci, 13(6): 664–666 Ma D K, Jang M H, Guo J U, Kitabatake Y, Chang M L, Pow-Anpongkul N, Flavell R A, Lu B, Ming G L, Song H (2009). Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science, 323(5917): 1074–1077 Chen W G, Chang Q, Lin Y, Meissner A, West A E, Griffith E C, Jaenisch R, Greenberg M E (2003). Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science, 302(5646): 885–889 Zhou Z, Hong E J, Cohen S, Zhao WN, Ho H Y, Schmidt L, Chen WG, Lin Y, Savner E, Griffith E C, Hu L, Steen J A, Weitz C J, Greenberg M E (2006). Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron, 52(2): 255–269 Kaas G A, Zhong C, Eason D E, Ross D L, Vachhani R V, Ming G L, King J R, Song H, Sweatt J D (2013). TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation. Neuron, 79(6): 1086–1093 Zhu T, Liang C, Li D, Tian M, Liu S, Gao G, Guan J S (2016). Histone methyltransferase Ash1L mediates activity-dependent repression of neurexin-1a. Sci Rep, 6(1): 26597 Ding X, Liu S, Tian M, Zhang W, Zhu T, Li D, Wu J, Deng H, Jia Y, Xie W, Xie H, Guan J S (2017). Activity-induced histone modifications govern Neurexin-1 mRNA splicing and memory preservation. Nat Neurosci, 20(5): 690–699 Su Y, Shin J, Zhong C, Wang S, Roychowdhury P, Lim J, Kim D, Ming G L, Song H (2017). Neuronal activity modifies the chromatin accessibility landscape in the adult brain. Nat Neurosci, 20(3): 476–483 Rudenko A, Dawlaty M M, Seo J, Cheng AW, Meng J, Le T, Faull K F, Jaenisch R, Tsai L H (2013). Tet1 is critical for neuronal activityregulated gene expression and memory extinction. Neuron, 79(6): 1109–1122 Gräff J, Joseph N F, Horn M E, Samiei A, Meng J, Seo J, Rei D, Bero A W, Phan T X, Wagner F, Holson E, Xu J, Sun J, Neve R L, Mach R H, Haggarty S J, Tsai L H (2014). Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories. Cell, 156(1-2): 261–276 Zovkic I B, Paulukaitis B S, Day J J, Etikala D M, Sweatt J D (2014). Histone H2A.Z subunit exchange controls consolidation of recent and remote memory. Nature, 515(7528): 582–586 Halder R, Hennion M, Vidal R O, Shomroni O, Rahman R U, Rajput A, Centeno T P, van Bebber F, Capece V, Garcia Vizcaino J C, Schuetz A L, Burkhardt S, Benito E, Navarro Sala M, Javan S B, Haass C, Schmid B, Fischer A, Bonn S (2016). DNA methylation changes in plasticity genes accompany the formation and maintenance of memory. Nat Neurosci, 19(1): 102–110 Nelson E D, Kavalali E T, Monteggia L M (2008). Activity-dependent suppression of miniature neurotransmission through the regulation of DNA methylation. J Neurosci, 28(2): 395–406 Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T, Kandel E R (2012). A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell, 149(3): 693–707 Meadows J P, Guzman-Karlsson M C, Phillips S, Holleman C, Posey J L, Day J J, Hablitz J J, Sweatt J D (2015). DNA methylation regulates neuronal glutamatergic synaptic scaling. Sci Signal, 8(382): ra61 Südhof T C (2008). Neuroligins and neurexins link synaptic function to cognitive disease. Nature, 455(7215): 903–911 Banerjee T, Chakravarti D (2011). A peek into the complex realm of histone phosphorylation. Mol Cell Biol, 31(24): 4858–4873 Goll M G, Bestor T H (2005). Eukaryotic cytosine methyltransferases. Annu Rev Biochem, 74(1): 481–514 Su, Y., Shin, J., Zhong, C. & Wang, S. Neuronal activity modifies the chromatin accessibility landscape in the adult brain. 20, 476–483, doi:10.1038/nn.4494 (2017). Guo J U, Su Y, Zhong C, Ming G L, Song H (2011). Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond. Cell Cycle, 10(16): 2662–2668 59 (!!! INVALID CITATION !!!). Batsché E, Yaniv M, Muchardt C (2006). The human SWI/SNF subunit Brm is a regulator of alternative splicing. Nat Struct Mol Biol, 13(1): 22–29 Martinez E, Palhan V B, Tjernberg A, Lymar E S, Gamper A M, Kundu T K, Chait B T, Roeder R G (2001). Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. Mol Cell Biol, 21(20): 6782–6795 Cheng D, Côté J, Shaaban S, Bedford M T (2007). The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing. Mol Cell, 25(1): 71–83 Kolasinska-Zwierz P, Down T, Latorre I, Liu T, Liu X S, Ahringer J (2009). Differential chromatin marking of introns and expressed exons by H3K36me3. Nat Genet, 41(3): 376–381 Spies N, Nielsen C B, Padgett R A, Burge C B (2009). Biased chromatin signatures around polyadenylation sites and exons. Mol Cell, 36(2): 245–254 Andersson R, Enroth S, Rada-Iglesias A, Wadelius C, Komorowski J (2009). Nucleosomes are well positioned in exons and carry characteristic histone modifications. Genome Res, 19(10): 1732–1741 Schwartz S, Meshorer E, Ast G (2009). Chromatin organization marks exon-intron structure. Nat Struct Mol Biol, 16(9): 990–995 Luco R F, Pan Q, Tominaga K, Blencowe B J, Pereira-Smith O M, Misteli T (2010). Regulation of alternative splicing by histone modifications. Science, 327(5968): 996–1000 Nogues G, Kadener S, Cramer P, Bentley D, Kornblihtt A R (2002). Transcriptional activators differ in their abilities to control alternative splicing. J Biol Chem, 277(45): 43110–43114 Schor I E, Rascovan N, Pelisch F, Alló M, Kornblihtt A R (2009). Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proc Natl Acad Sci USA, 106(11): 4325–4330 Sims R J 3rd, Millhouse S, Chen C F, Lewis B A, Erdjument-Bromage H, Tempst P, Manley J L, Reinberg D (2007). Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing. Mol Cell, 28(4): 665–676 Piacentini L, Fanti L, Negri R, Del Vescovo V, Fatica A, Altieri F, Pimpinelli S (2009). Heterochromatin protein 1 (HP1a) positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila. PLoS Genet, 5(10): e1000670 Luco R F, Allo M, Schor I E, Kornblihtt A R, Misteli T (2011). Epigenetics in alternative pre-mRNA splicing. Cell, 144(1): 16–26 Rountree M R, Bachman K E, Herman J G, Baylin S B (2001). DNA methylation, chromatin inheritance, and cancer. Oncogene, 20(24): 3156–3165 Probst A V, Dunleavy E, Almouzni G (2009). Epigenetic inheritance during the cell cycle. Nat Rev Mol Cell Biol, 10(3): 192–206 Okano M, Bell D W, Haber D A, Li E (1999). DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 99(3): 247–257 Jia D, Jurkowska R Z, Zhang X, Jeltsch A, Cheng X (2007). Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature, 449(7159): 248–251 Pollack Y, Stein R, Razin A, Cedar H (1980). Methylation of foreign DNA sequences in eukaryotic cells. Proc Natl Acad Sci USA, 77(11): 6463–6467 Wigler M, Levy D, Perucho M (1981). The somatic replication of DNA methylation. Cell, 24(1): 33–40 Gruenbaum Y, Cedar H, Razin A (1982). Substrate and sequence specificity of a eukaryotic DNA methylase. Nature, 295(5850): 620–622 Cheng X (2014). Structural and functional coordination of DNA and histone methylation. Cold Spring Harb Perspect Biol, 6(8): a018747 Kimura H, Shiota K (2003). Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1. J Biol Chem, 278(7): 4806–4812 Reik W (2007). Stability and flexibility of epigenetic gene regulation in mammalian development. Nature, 447(7143): 425–432 Nakatani Y, Ray-Gallet D, Quivy J P, Tagami H, Almouzni G (2004). Two distinct nucleosome assembly pathways: dependent or independent of DNA synthesis promoted by histone H3.1 and H3.3 complexes. Cold Spring Harb Symp Quant Biol, 69(0): 273–280 Bannister A J, Zegerman P, Partridge J F, Miska E A, Thomas J O, Allshire R C, Kouzarides T (2001). Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature, 410(6824): 120–124 Lachner M, O’Carroll D, Rea S, Mechtler K, Jenuwein T (2001). Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature, 410(6824): 116–120 Fritsch L, Robin P, Mathieu J R, Souidi M, Hinaux H, Rougeulle C, Harel-Bellan A, Ameyar-Zazoua M, Ait-Si-Ali S (2010). A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. Mol Cell, 37(1): 46–56 Hansen K H, Helin K (2009). Epigenetic inheritance through selfrecruitment of the polycomb repressive complex 2. Epigenetics, 4(3): 133–138 Margueron R, Justin N, Ohno K, Sharpe M L, Son J, Drury W J 3rd, Voigt P, Martin S R, Taylor W R, De Marco V, Pirrotta V, Reinberg D, Gamblin S J (2009). Role of the polycomb protein EED in the propagation of repressive histone marks. Nature, 461(7265): 762–767 Vaute O, Nicolas E, Vandel L, Trouche D (2002). Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases. Nucleic Acids Res, 30(2): 475–481 Scharf A N, Meier K, Seitz V, Kremmer E, Brehm A, Imhof A (2009). Monomethylation of lysine 20 on histone H4 facilitates chromatin maturation. Mol Cell Biol, 29(1): 57–67 Fuks F, Burgers W A, Brehm A, Hughes-Davies L, Kouzarides T (2000). DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat Genet, 24(1): 88–91 Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, Chiba T, Nakao M (2003). Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem, 278(26): 24132–24138 Dietrich J, Han R, Yang Y, Mayer-Pröschel M, Noble M (2006). CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol, 5(7): 22 Mizutani K, Yoon K, Dang L, Tokunaga A, Gaiano N (2007). Differential Notch signalling distinguishes neural stem cells from intermediate progenitors. Nature, 449(7160): 351–355 Namihira M, Kohyama J, Abematsu M, Nakashima K (2008). Epigenetic mechanisms regulating fate specification of neural stem cells. Philos Trans R Soc Lond B Biol Sci, 363(1500): 2099–2109 Hirabayashi Y, Gotoh Y (2010). Epigenetic control of neural precursor cell fate during development. Nat Rev Neurosci, 11(6): 377–388 Lunyak V V, Burgess R, Prefontaine G G, Nelson C, Sze S H, Chenoweth J, Schwartz P, Pevzner P A, Glass C, Mandel G, Rosenfeld M G (2002). Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science, 298(5599): 1747–1752 Ballas N, Grunseich C, Lu D D, Speh J C, Mandel G (2005). REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell, 121(4): 645–657 Sikorska M, Sandhu J K, Deb-Rinker P, Jezierski A, Leblanc J, Charlebois C, Ribecco-Lutkiewicz M, Bani-Yaghoub M, Walker P R (2008). Epigenetic modifications of SOX2 enhancers, SRR1 and SRR2, correlate with in vitro neural differentiation. J Neurosci Res, 86(8): 1680–1693 Sun Y, Nadal-Vicens M, Misono S, Lin M Z, Zubiaga A, Hua X, Fan G, Greenberg M E (2001). Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms. Cell, 104 (3): 365–376 Takizawa T, Nakashima K, Namihira M, Ochiai W, Uemura A, Yanagisawa M, Fujita N, Nakao M, Taga T (2001). DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain. Dev Cell, 1(6): 749–758 Namihira M, Nakashima K, Taga T (2004). Developmental stage dependent regulation of DNA methylation and chromatin modification in a immature astrocyte specific gene promoter. FEBS Lett, 572 (1-3): 184–188 Fan G, Martinowich K, Chin M H, He F, Fouse S D, Hutnick L, Hattori D, Ge W, Shen Y, Wu H, ten Hoeve J, Shuai K, Sun Y E (2005). DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Development, 132(15): 3345–3356 Brooks P J, Marietta C, Goldman D (1996). DNA mismatch repair and DNA methylation in adult brain neurons. J Neurosci, 16(3): 939–945 Wu Z, Huang K, Yu J, Le T, Namihira M, Liu Y, Zhang J, Xue Z, Cheng L, Fan G (2012). Dnmt3a regulates both proliferation and differentiation of mouse neural stem cells. J Neurosci Res, 90(10): 1883–1891 Bai S, Ghoshal K, Datta J, Majumder S, Yoon S O, Jacob S T (2005). DNA methyltransferase 3b regulates nerve growth factor-induced differentiation of PC12 cells by recruiting histone deacetylase 2. Mol Cell Biol, 25(2): 751–766 Williams R R, Azuara V, Perry P, Sauer S, Dvorkina M, Jørgensen H, Roix J, McQueen P, Misteli T, Merkenschlager M, Fisher A G (2006). Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus. J Cell Sci, 119(Pt 1): 132–140 Attia M, Rachez C, De Pauw A, Avner P, Rogner U C (2007). Nap1l2 promotes histone acetylation activity during neuronal differentiation. Mol Cell Biol, 27(17): 6093–6102 Gogolla N, Leblanc J J, Quast K B, Südhof T C, Fagiolini M, Hensch T K (2009). Common circuit defect of excitatory-inhibitory balance in mouse models of autism. J Neurodev Disord, 1(2): 172–181 Geschwind D H, Levitt P (2007). Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol, 17 (1): 103–111 Wood L, Shepherd G M (2010). Synaptic circuit abnormalities of motorfrontal layer 2/3 pyramidal neurons in a mutant mouse model of Rett syndrome. Neurobiol Dis, 38(2): 281–287 Ho L, Crabtree G R (2010). Chromatin remodelling during development. Nature, 463(7280): 474–484 Ronan J L, Wu W, Crabtree G R (2013). From neural development to cognition: unexpected roles for chromatin. Nat Rev Genet, 14(5): 347–359 Yamada T, Yang Y, Hemberg M, Yoshida T, Cho H Y, Murphy J P, Fioravante D, Regehr W G, Gygi S P, Georgopoulos K, Bonni A (2014). Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain. Neuron, 83(1): 122–134 Yang Y, Yamada T, Hill K K, Hemberg M, Reddy N C, Cho H Y, Guthrie A N, Oldenborg A, Heiney S A, Ohmae S, Medina J F, Holy T E, Bonni A (2016). Chromatin remodeling inactivates activity genes and regulates neural coding. Science, 353(6296): 300–305 Fortin D A, Srivastava T, Soderling T R (2012). Structural modulation of dendritic spines during synaptic plasticity. Neuroscientist, 18(4): 326–341 Chen D Y, Bambah-Mukku D, Pollonini G, Alberini C M (2012). Glucocorticoid receptors recruit the CaMKIIa-BDNF-CREB pathways to mediate memory consolidation. Nat Neurosci, 15(12): 1707–1714 Ding, X.et alActivity-induced histone modifications govern Neurexin-1 mRNA splicing and memory preservation. 20, 690–699 (2017). Maze I, Wenderski W, Noh K M, Bagot R C, Tzavaras N, Purushothaman I, Elsässer S J, Guo Y, Ionete C, Hurd Y L, Tamminga C A, Halene T, Farrelly L, Soshnev A A, Wen D, Rafii S, Birtwistle M R, Akbarian S, Buchholz B A, Blitzer R D, Nestler E J, Yuan Z F, Garcia B A, Shen L, Molina H, Allis C D (2015). Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. Neuron, 87(1): 77–94 Levenson J M, Roth T L, Lubin F D, Miller C A, Huang I C, Desai P, Malone L M, Sweatt J D (2006). Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J Biol Chem, 281(23): 15763–15773 Morris MJ, Adachi M, Na E S, Monteggia LM(2014). Selective role for DNMT3a in learning and memory. Neurobiol Learn Mem, 115: 30–37 Mitchnick K A, Creighton S, O’Hara M, Kalisch B E, Winters B D (2015). Differential contributions of de novo and maintenance DNA methyltransferases to object memory processing in the rat hippocampus and perirhinal cortex–a double dissociation. Eur J Neurosci, 41(6): 773–786 Kamakaka R T, Biggins S (2005). Histone variants: deviants? Genes Dev, 19(3): 295–310 Kendler K S (2001). Twin studies of psychiatric illness: an update. Arch Gen Psychiatry, 58(11): 1005–1014 Millan M J, Agid Y, Brüne M, Bullmore E T, Carter C S, Clayton N S, Connor R, Davis S, Deakin B, DeRubeis R J, Dubois B, Geyer M A, Goodwin G M, Gorwood P, Jay T M, Joëls M, Mansuy I M, Meyer-Lindenberg A, Murphy D, Rolls E, Saletu B, Spedding M, Sweeney J, Whittington M, Young L J (2012). Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov, 11(2): 141–168 Gibson G (2012). Rare and common variants: twenty arguments. Nat Rev Genet, 13(2): 135–145 Eichler E E, Flint J, Gibson G, Kong A, Leal S M, Moore J H, Nadeau J H (2010). Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet, 11(6): 446–450 Gershon E S, Alliey-Rodriguez N, Liu C (2011). After GWAS: searching for genetic risk for schizophrenia and bipolar disorder. Am J Psychiatry, 168(3): 253–256 So H C, Gui A H, Cherny S S, Sham P C (2011). Evaluating the heritability explained by known susceptibility variants: a survey of ten complex diseases. Genet Epidemiol, 35(5): 310–317 BohacekJ, Mansuy I M(2013).Epigenetic inheritance of disease and disease risk. Neuropsychopharmacology, 38: 220–236 Danchin É, Charmantier A, Champagne F A, Mesoudi A, Pujol B, Blanchet S (2011). Beyond DNA: integrating inclusive inheritance into an extended theory of evolution. Nat Rev Genet, 12(7): 475–486 Daxinger L, Whitelaw E (2010). Transgenerational epigenetic inheritance: more questions than answers. Genome Res, 20(12): 1623–1628 Horsthemke B (2007). Heritable germline epimutations in humans. Nat Genet, 39(5): 573–574, author reply 575–576 Sha K (2008). A mechanistic view of genomic imprinting. Annu Rev Genomics Hum Genet, 9(1): 197–216 Paoloni-Giacobino A, Chaillet J R (2006). The role of DMDs in the maintenance of epigenetic states. Cytogenet Genome Res, 113(1-4): 116–121 Bartolomei M S, Ferguson-Smith A C (2011). Mammalian genomic imprinting. Cold Spring Harb Perspect Biol, 3(7): a002592 Feng S, Jacobsen S E, Reik W (2010). Epigenetic reprogramming in plant and animal development. Science, 330(6004): 622–627 Franklin T B, Russig H, Weiss I C, Gräff J, Linder N, Michalon A, Vizi S, Mansuy IM(2010). Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry, 68(5): 408–415 Johnson G D, Lalancette C, Linnemann A K, Leduc F, Boissonneault G, Krawetz S A (2011). The sperm nucleus: chromatin, RNA, and he nuclear matrix. Reproduction, 141(1): 21–36 Hammoud S S, Nix D A, Zhang H, Purwar J, Carrell D T, Cairns B R (2009). Distinctive chromatin in human sperm packages genes for embryo development. Nature, 460(7254): 473–478 Puri D, Dhawan J, Mishra R K (2010). The paternal hidden agenda: Epigenetic inheritance through sperm chromatin. Epigenetics, 5(5): 386–391 Brykczynska U, Hisano M, Erkek S, Ramos L, Oakeley E J, Roloff T C, Beisel C, Schübeler D, Stadler M B, Peters A H (2010). Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol, 17(6): 679–687 Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen L A Ozonoff S, Lajonchere C, Grether J K, Risch N (2011). Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry, 68(11): 1095–1102 Cannon T D, Kaprio J, Lönnqvist J, Huttunen M, Koskenvuo M (1998). The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study. Arch Gen Psychiatry, 55(1): 67–74 Gatz M, Pedersen N L, Berg S, Johansson B, Johansson K, Mortimer J A, Posner S F, Viitanen M, Winblad B, Ahlbom A (1997). Heritability for Alzheimer’s disease: the study of dementia in Swedish twins. J Gerontol A Biol Sci Med Sci, 52(2): M117–M125 Fraga M F, Ballestar E, Paz M F, Ropero S, Setien F, Ballestar M L, Heine-Suñer D, Cigudosa J C, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector T D, Wu Y Z, Plass C, Esteller M (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA, 102(30): 10604–10609 Gershon A, Sudheimer K, Tirouvanziam R, Williams L M, O’Hara R (2013). The long-term impact of early adversity on late-life psychiatric disorders. Curr Psychiatry Rep, 15(4): 352 Bagot R C, Zhang T Y, Wen X, Nguyen T T, Nguyen H B, Diorio J, Wong T P, Meaney M J (2012). Variations in postnatal maternal care and the epigenetic regulation of metabotropic glutamate receptor 1 expression and hippocampal function in the rat. Proc Natl Acad Sci USA, 109(Suppl 2): 17200–17207 Zhang T Y, Hellstrom I C, Bagot R C, Wen X, Diorio J, Meaney M J (2010). Maternal care and DNA methylation of a glutamic acid decarboxylase 1 promoter in rat hippocampus. J Neurosci, 30(39): 13130–13137 Roth T L, Lubin F D, Funk A J, Sweatt J D (2009). Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry, 65(9): 760–769 Hashimoto T, Bergen S E, Nguyen Q L, Xu B, Monteggia L M, Pierri J N, Sun Z, Sampson A R, Lewis D A (2005). Relationship of brainderived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia. J Neurosci, 25(2): 372–383 Jin B, Tao Q, Peng J, Soo H M, Wu W, Ying J, Fields C R, Delmas A L, Liu X, Qiu J, Robertson K D (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): 690–709 Jowaed A, Schmitt I, Kaut O, Wüllner U (2010). Methylation regulates alpha-synuclein expression and is decreased in Parkinson’s disease patients’ brains. J Neurosci, 30(18): 6355–6359 Winkelmann J, Lin L, Schormair B, Kornum B R, Faraco J, Plazzi G, Melberg A, Cornelio F, Urban A E, Pizza F, Poli F, Grubert F, Wieland T, Graf E, Hallmayer J, Strom T M, Mignot E (2012). Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum Mol Genet, 21(10): 2205–2210 Chestnut B A, Chang Q, Price A, Lesuisse C, Wong M, Martin L J (2011). Epigenetic regulation of motor neuron cell death through DNA methylation. J Neurosci, 31(46): 16619–16636 Amir R E, Van den Veyver I B, Wan M, Tran C Q, Francke U, Zoghbi H Y (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein2. Nat Genet, 23(2): 185–188 Mnatzakanian G N, Lohi H, Munteanu I, Alfred S E, Yamada T, MacLeod P J, Jones J R, Scherer S W, Schanen N C, Friez M J, Vincent J B, Minassian B A (2004). A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome. Nat Genet, 36(4): 339–341 Chen R Z, Akbarian S, Tudor M, Jaenisch R (2001). Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet, 27(3): 327–331 Collins A L, Levenson J M, Vilaythong A P, Richman R, Armstrong D L, Noebels J L, David Sweatt J, Zoghbi H Y (2004). Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet, 13(21): 2679–2689 Guy J, Hendrich B, Holmes M, Martin J E, Bird A (2001). A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet, 27(3): 322–326 Carney R M, Wolpert C M, Ravan S A, Shahbazian M, Ashley-Koch A, Cuccaro M L, Vance J M, Pericak-Vance M A (2003). Identification of MeCP2 mutations in a series of females with autistic disorder. Pediatr Neurol, 28(3): 205–211 Kleefstra T, van Zelst-Stams W A, Nillesen W M, Cormier-Daire V, Houge G, Foulds N, van Dooren M, Willemsen M H, Pfundt R, Turner A, Wilson M, McGaughran J, Rauch A, Zenker M, Adam M P, Innes M, Davies C, López A G, Casalone R, Weber A, Brueton L A, Navarro A D, Bralo M P, Venselaar H, Stegmann S P, Yntema H G, van Bokhoven H, Brunner H G (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(9): 598–606 Kirov G, Pocklington A J, Holmans P, Ivanov D, Ikeda M, Ruderfer D, Moran J, Chambert K, Toncheva D, Georgieva L, Grozeva D, Fjodorova M, Wollerton R, Rees E, Nikolov I, van de Lagemaat L N, Bayés A, Fernandez E, Olason P I, Böttcher Y, Komiyama N H, Collins M O, Choudhary J, Stefansson K, Stefansson H, Grant S G, Purcell S, Sklar P, O’Donovan M C, Owen M J (2012). De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol Psychiatry, 17(2): 142–153 Roelfsema J H, Peters D J (2007). Rubinstein-Taybi syndrome: clinical and molecular overview. Expert Rev Mol Med, 9(23): 1–16 Zollino M, Orteschi D, Murdolo M, Lattante S, Battaglia D, Stefanini C, Mercuri E, Chiurazzi P, Neri G, Marangi G (2012). Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype. Nat Genet, 44(6): 636–638 Michelson D J, Shevell M I, Sherr E H, Moeschler J B, Gropman A L, Ashwal S (2011). Evidence report: Genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology, 77(17): 1629–1635 Adegbola A, Gao H, Sommer S, Browning M (2008). A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD). Am J Med Genet A, 146A(4): 505–511 Berdasco M, Ropero S, Setien F, Fraga M F, Lapunzina P, Losson R, Alaminos M, Cheung N K, 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): 21830–21835 Kleine-Kohlbrecher D, Christensen J, Vandamme J, Abarrategui I, Bak M, Tommerup N, Shi X, Gozani O, Rappsilber J, Salcini A E, 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): 165–178 Pereira P M, Schneider A, Pannetier S, Heron D, Hanauer A (2010). Coffin-Lowry syndrome. Eur J Hum Genet, 18(6): 627–633 Gibson W T, Hood R L, Zhan S H, Bulman D E, Fejes A P, Moore R, Mungall A J, Eydoux P, Babul-Hirji R, An J, Marra MA, Chitayat D, Boycott K M, Weaver D D, Jones S J, and the FORGE Canada Consortium (2012). Mutations in EZH2 causeWeaver syndrome. Am J Hum Genet, 90(1): 110–118 Jones W D, Dafou D, McEntagart M, Woollard W J, Elmslie F V, Holder-Espinasse M, Irving M, Saggar A K, Smithson S, Trembath R C, Deshpande C, Simpson M A (2012). De novo mutations in MLL cause Wiedemann-Steiner syndrome. Am J Hum Genet, 91(2): 358–364 Ng S B, Bigham A W, Buckingham K J, Hannibal M C, McMillin M J, Gildersleeve H I, Beck A E, Tabor H K, Cooper G M, Mefford H C, Lee C, Turner E H, Smith J D, Rieder M J, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson D A, Bamshad M J, Shendure J (2010). Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet, 42(9): 790–793 Campeau PM, Kim J C, Lu J T, Schwartzentruber J A, Abdul-Rahman O A, Schlaubitz S, Murdock D M, Jiang M M, Lammer E J, Enns G M, Rhead WJ, Rowland J, Robertson S P, Cormier-Daire V, Bainbridge M N, Yang X J, Gingras M C, Gibbs R A, Rosenblatt D S, Majewski J, Lee B H (2012). Mutations in KAT6B, encoding a histone acetyltransferase, cause Genitopatellar syndrome. Am J Hum Genet, 90(2): 282–289 Lederer D, Grisart B, Digilio M C, Benoit V, Crespin M, Ghariani S C, 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(1): 119–124 Williams S R, Aldred M A, Der Kaloustian V M, Halal F, Gowans G, McLeod D R, Zondag S, Toriello H V, Magenis R E, Elsea S H (2010). Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems. Am J Hum Genet, 87(2): 219–228 Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, Yamrom B, Lee Y H, Narzisi G, Leotta A, Kendall J, Grabowska E, Ma B, Marks S, Rodgers L, Stepansky A, Troge J, Andrews P, Bekritsky M, Pradhan K, Ghiban E, Kramer M, Parla J, Demeter R, Fulton L L, Fulton R S, Magrini V J, Ye K, Darnell J C, Darnell R B, Mardis E R, Wilson R K, Schatz M C, McCombie W R, Wigler M (2012). De novo gene disruptions in children on the autistic spectrum. Neuron, 74(2): 285–299 Steffan J S, Bodai L, Pallos J, Poelman M, McCampbell A, Apostol B L, Kazantsev A, Schmidt E, Zhu Y Z, Greenwald M, Kurokawa R, Housman D E, Jackson G R, Marsh J L, Thompson L M (2001). Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature, 413(6857): 739–743 Ferrante R J, Kubilus J K, Lee J, Ryu H, Beesen A, Zucker B, Smith K, Kowall NW, Ratan R R, Luthi-Carter R, Hersch SM(2003). Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington’s disease mice. J Neurosci, 23(28): 9418–9427 Richards C, Jones C, Groves L, Moss J, Oliver C (2015). Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis. Lancet Psychiatry, 2(10): 909–916 Beyer K S, Blasi F, Bacchelli E, Klauck S M, Maestrini E, Poustka A, Molecular Genetic Study of Autism C I, and the International Molecular Genetic Study of Autism Consortium (IMGSAC) (2002). Mutation analysis of the coding sequence of the MECP2 gene in infantile autism. Hum Genet, 111(4-5): 305–309 Crawford D C, Acuna J M, Sherman S L(2001). FMR1 and the fragile X syndrome: human genome epidemiology review. Genet Med, 3: 359–371 Bernier R, Golzio C, Xiong B, Stessman H A, Coe B P, Penn O, Witherspoon K, Gerdts J, Baker C, Vulto-van Silfhout A T, Schuurs-Hoeijmakers J H, Fichera M, Bosco P, Buono S, Alberti A, Failla P, Peeters H, Steyaert J, Vissers L E, Francescatto L, Mefford H C, Rosenfeld J A, Bakken T, O’Roak B J, Pawlus M, Moon R, Shendure J, Amaral D G, Lein E, Rankin J, Romano C, de Vries B B, Katsanis N, Eichler E E (2014). Disruptive CHD8 mutations define a subtype of autism early in development. Cell, 158(2): 263–276 Merner N, Forgeot d’Arc B, Bell S C, Maussion G, Peng H, Gauthier J, Crapper L, Hamdan F F, Michaud J L, Mottron L, Rouleau G A, Ernst C (2016). A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): A case report and literature review. Am J Med Genet A, 170A(5): 1225–1235 Johansson M, Råstam M, Billstedt E, Danielsson S, Strömland K, Miller M, Gillberg C (2006). Autism spectrum disorders and underlying brain pathology in CHARGE association. Dev Med Child Neurol, 48 (1): 40–50 Smith I M, Nichols S L, Issekutz K, Blake K, and the Canadian Paediatric Surveillance Program (2005). Behavioral profiles and symptoms of autism in CHARGE syndrome: preliminary Canadian epidemiological data. Am J Med Genet A, 133A(3): 248–256 Ladd-Acosta C, Hansen K D, Briem E, Fallin M D, Kaufmann W E, Feinberg A P (2014). Common DNA methylation alterations in multiple brain regions in autism. Mol Psychiatry, 19(8): 862–871 Nardone S, Sams D S, Reuveni E, Getselter D, Oron O, Karpuj M, Elliott E (2014). DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways. Transl Psychiatry, 4(9): e433 Elagoz Yuksel M, Yuceturk B, Karatas O F, Ozen M, Dogangun B (2016). The altered promoter methylation of oxytocin receptor gene in autism. J Neurogenet, 30(3-4): 280–284 Gregory S G, Connelly J J, Towers A J, Johnson J, Biscocho D, Markunas C A, Lintas C, Abramson R K, Wright H H, Ellis P, Langford C F, Worley G, Delong G R, Murphy S K, Cuccaro M L, Persico A, Pericak-Vance M A (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med, 7(1): 62 Jiang Y H, Sahoo T, Michaelis R C, Bercovich D, Bressler J, Kashork C D, Liu Q, Shaffer L G, Schroer R J, Stockton D W, Spielman R S, Stevenson R E, Beaudet A L (2004). A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A. Am J Med Genet A, 131(1): 1–10 Nagarajan R P, Hogart A R, Gwye Y, Martin M R, LaSalle J M (2006). Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics, 1(4): e1–e11 Zhu L, Wang X, Li X L, Towers A, Cao X, Wang P, Bowman R, Yang H, Goldstein J, Li Y J, Jiang Y H (2014). Epigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders. Hum Mol Genet, 23(6): 1563–1578 Shulha H P, Cheung I, Whittle C, Wang J, Virgil D, Lin C L, Guo Y, Lessard A, Akbarian S, Weng Z (2012). Epigenetic signatures of autism: trimethylated H3K4 landscapes in prefrontal neurons. Arch Gen Psychiatry, 69(3): 314–324 Sun W, Poschmann J, Cruz-Herrera Del Rosario R, Parikshak N N, Hajan H S, Kumar V, Ramasamy R, Belgard T G, Elanggovan B, Wong C C, Mill J, Geschwind D H, Prabhakar S (2016). Histone Acetylome-wide Association Study of Autism Spectrum Disorder. Cell, 167(5): 1385–1397.e11 Hernandez D G, Nalls M A, Gibbs J R, Arepalli S, van der Brug M, Chong S, Moore M, Longo D L, Cookson M R, Traynor B J, Singleton A B (2011). Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum Mol Genet, 20(6): 1164–1172 Lu H, Liu X, Deng Y, Qing H (2013). DNA methylation, a hand behind neurodegenerative diseases. Front Aging Neurosci, 5: 85 Lu T, Aron L, Zullo J, Pan Y, Kim H, Chen Y, Yang T H, Kim H M, Drake D, Liu X S, Bennett D A, Colaiácovo M P, Yankner B A (2014). REST and stress resistance in ageing and Alzheimer’s disease. Nature, 507(7493): 448–454 De Jager P L, Srivastava G, Lunnon K, Burgess J, Schalkwyk L C, Yu L, EatonML, Keenan B T, Ernst J, McCabe C, Tang A, Raj T, Replogle J, Brodeur W, Gabriel S, Chai H S, Younkin C, Younkin S G, Zou F, Szyf M, Epstein C B, Schneider J A, Bernstein B E, Meissner A, Ertekin-Taner N, Chibnik L B, Kellis M, Mill J, Bennett D A (2014). Alzheimer’s disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat Neurosci, 17(9): 1156–1163 Lunnon K, Smith R, Hannon E, De Jager P L, Srivastava G, Volta M, Troakes C, Al-Sarraj S, Burrage J, Macdonald R, Condliffe D, Harries L W, Katsel P, Haroutunian V, Kaminsky Z, Joachim C, Powell J, Lovestone S, Bennett D A, Schalkwyk L C, Mill J (2014). Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease. Nat Neurosci, 17(9): 1164–1170 Chouliaras L, Mastroeni D, Delvaux E, Grover A, Kenis G, Hof P R, Steinbusch H W, Coleman P D, Rutten B P, van den Hove D L (2013). Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer’s disease patients. Neurobiol Aging, 34(9): 2091–2099 Mastroeni D, McKee A, Grover A, Rogers J, Coleman P D (2009). Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer’s disease. PLoS One, 4(8): e6617 Wang S C, Oelze B, Schumacher A (2008). Age-specific epigenetic drift in late-onset Alzheimer’s disease. PLoS One, 3(7): e2698 Bakulski K M, Dolinoy D C, Sartor M A, Paulson H L, Konen J R, Lieberman A P, Albin R L, Hu H, Rozek L S (2012). Genome-wide DNA methylation differences between late-onset Alzheimer’s disease and cognitively normal controls in human frontal cortex. J Alzheimers Dis, 29(3): 571–588 Savas J N, Makusky A, Ottosen S, Baillat D, Then F, Krainc D, Shiekhattar R, Markey S P, Tanese N (2008). Huntington’s disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies. Proc Natl Acad Sci USA, 105(31): 10820–10825 Buckley N J, Johnson R, Zuccato C, Bithell A, Cattaneo E (2010). The role of REST in transcriptional and epigenetic dysregulation in Huntington’s disease. Neurobiol Dis, 39(1): 28–39 Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt B R, Hayden M R, Timmusk T, Rigamonti D, Cattaneo E (2003). Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet, 35(1): 76–83 Zuccato C, Belyaev N, Conforti P, Ooi L, Tartari M, Papadimou E, MacDonald M, Fossale E, Zeitlin S, Buckley N, Cattaneo E (2007). Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington’s disease. J Neurosci, 27(26): 6972–6983 von Schimmelmann M, Feinberg P A, Sullivan J M, Ku S M, Badimon A, Duff M K, Wang Z, Lachmann A, Dewell S, Ma’ayan A, Han M H, Tarakhovsky A, Schaefer A (2016). Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration. Nat Neurosci, 19(10): 1321–1330 Wang F, Yang Y, Lin X, Wang J Q, Wu Y S, Xie W, Wang D, Zhu S, Liao Y Q, Sun Q, Yang Y G, Luo H R, Guo C, Han C, Tang T S (2013). Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntington’s disease. Hum Mol Genet, 22(18): 3641–3653