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Epigenetic regulators sculpt the plastic brain

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  • Published:
Frontiers in Biology

Abstract

Background

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.

Objective

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.

Methods

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.”

Results

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.

Conclusion

Activity-dependent epigenetic mechanisms of gene expression regulation contribute to basic neuronal physiology, and defects were associated with an elevated risk for brain disorders.

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References

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Waddington C H (2012). The epigenotype. 1942. Int J Epidemiol, 41(1): 10–13

    Article  CAS  PubMed  Google Scholar 

  • Bird A (2007). Perceptions of epigenetics. Nature, 447(7143): 396–398

    Article  CAS  PubMed  Google Scholar 

  • Bird A (2002). DNA methylation patterns and epigenetic memory. Genes Dev, 16(1): 6–21

    Article  CAS  PubMed  Google Scholar 

  • Laird P W (2003). The power and the promise of DNA methylation markers. Nat Rev Cancer, 3(4): 253–266

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matzke M A, Birchler J A (2005). RNAi-mediated pathways in the nucleus. Nat Rev Genet, 6(1): 24–35

    Article  CAS  PubMed  Google Scholar 

  • Jenuwein T, Allis C D (2001). Translating the histone code. Science, 293 (5532): 1074–1080

    Article  CAS  PubMed  Google Scholar 

  • Kouzarides T (2007). Chromatin modifications and their function. Cell, 128(4): 693–705

    Article  CAS  PubMed  Google Scholar 

  • Pusarla R H, Bhargava P (2005). Histones in functional diversification. Core histone variants. FEBS J, 272(20): 5149–5168

    Article  CAS  PubMed  Google Scholar 

  • Talbert P B, Henikoff S (2010). Histone variants–ancient wrap artists of the epigenome. Nat Rev Mol Cell Biol, 11(4): 264–275

    Article  CAS  PubMed  Google Scholar 

  • Becker P B, Hörz W (2002). ATP-dependent nucleosome remodeling. Annu Rev Biochem, 71(1): 247–273

    Article  CAS  PubMed  Google Scholar 

  • Clapier C R, Cairns B R (2009). The biology of chromatin remodeling complexes. Annu Rev Biochem, 78(1): 273–304

    Article  CAS  PubMed  Google Scholar 

  • Borrelli E, Nestler E J, Allis C D, Sassone-Corsi P (2008). Decoding the epigenetic language of neuronal plasticity. Neuron, 60(6): 961–974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roth T L, Sweatt J D (2009). Regulation of chromatin structure in memory formation. Curr Opin Neurobiol, 19(3): 336–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sweatt J D (2016). GENE EXPRESSION. Chromatin controls behavior. Science, 353(6296): 218–219

    CAS  PubMed  Google Scholar 

  • Zovkic I B, Sweatt J D (2015). Memory-Associated Dynamic Regulation of the “Stable” Core of the Chromatin Particle. Neuron, 87(1): 1–4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sweatt J D (2013). The emerging field of neuroepigenetics. Neuron, 80 (3): 624–632

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller C A, Sweatt J D (2007). Covalent modification of DNA regulates memory formation. Neuron, 53(6): 857–869

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Südhof T C (2008). Neuroligins and neurexins link synaptic function to cognitive disease. Nature, 455(7215): 903–911

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Banerjee T, Chakravarti D (2011). A peek into the complex realm of histone phosphorylation. Mol Cell Biol, 31(24): 4858–4873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goll M G, Bestor T H (2005). Eukaryotic cytosine methyltransferases. Annu Rev Biochem, 74(1): 481–514

    Article  CAS  PubMed  Google Scholar 

  • 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).

    CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwartz S, Meshorer E, Ast G (2009). Chromatin organization marks exon-intron structure. Nat Struct Mol Biol, 16(9): 990–995

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rountree M R, Bachman K E, Herman J G, Baylin S B (2001). DNA methylation, chromatin inheritance, and cancer. Oncogene, 20(24): 3156–3165

    Article  CAS  PubMed  Google Scholar 

  • Probst A V, Dunleavy E, Almouzni G (2009). Epigenetic inheritance during the cell cycle. Nat Rev Mol Cell Biol, 10(3): 192–206

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wigler M, Levy D, Perucho M (1981). The somatic replication of DNA methylation. Cell, 24(1): 33–40

    Article  CAS  PubMed  Google Scholar 

  • Gruenbaum Y, Cedar H, Razin A (1982). Substrate and sequence specificity of a eukaryotic DNA methylase. Nature, 295(5850): 620–622

    Article  CAS  PubMed  Google Scholar 

  • Cheng X (2014). Structural and functional coordination of DNA and histone methylation. Cold Spring Harb Perspect Biol, 6(8): a018747

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Reik W (2007). Stability and flexibility of epigenetic gene regulation in mammalian development. Nature, 447(7143): 425–432

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Hansen K H, Helin K (2009). Epigenetic inheritance through selfrecruitment of the polycomb repressive complex 2. Epigenetics, 4(3): 133–138

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirabayashi Y, Gotoh Y (2010). Epigenetic control of neural precursor cell fate during development. Nat Rev Neurosci, 11(6): 377–388

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Brooks P J, Marietta C, Goldman D (1996). DNA mismatch repair and DNA methylation in adult brain neurons. J Neurosci, 16(3): 939–945

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Geschwind D H, Levitt P (2007). Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol, 17 (1): 103–111

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho L, Crabtree G R (2010). Chromatin remodelling during development. Nature, 463(7280): 474–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fortin D A, Srivastava T, Soderling T R (2012). Structural modulation of dendritic spines during synaptic plasticity. Neuroscientist, 18(4): 326–341

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding, X.et alActivity-induced histone modifications govern Neurexin-1 mRNA splicing and memory preservation. 20, 690–699 (2017).

    CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Morris MJ, Adachi M, Na E S, Monteggia LM(2014). Selective role for DNMT3a in learning and memory. Neurobiol Learn Mem, 115: 30–37

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Kamakaka R T, Biggins S (2005). Histone variants: deviants? Genes Dev, 19(3): 295–310

    Article  CAS  PubMed  Google Scholar 

  • Kendler K S (2001). Twin studies of psychiatric illness: an update. Arch Gen Psychiatry, 58(11): 1005–1014

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Gibson G (2012). Rare and common variants: twenty arguments. Nat Rev Genet, 13(2): 135–145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • BohacekJ, Mansuy I M(2013).Epigenetic inheritance of disease and disease risk. Neuropsychopharmacology, 38: 220–236

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Daxinger L, Whitelaw E (2010). Transgenerational epigenetic inheritance: more questions than answers. Genome Res, 20(12): 1623–1628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horsthemke B (2007). Heritable germline epimutations in humans. Nat Genet, 39(5): 573–574, author reply 575–576

    Article  CAS  PubMed  Google Scholar 

  • Sha K (2008). A mechanistic view of genomic imprinting. Annu Rev Genomics Hum Genet, 9(1): 197–216

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Bartolomei M S, Ferguson-Smith A C (2011). Mammalian genomic imprinting. Cold Spring Harb Perspect Biol, 3(7): a002592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng S, Jacobsen S E, Reik W (2010). Epigenetic reprogramming in plant and animal development. Science, 330(6004): 622–627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Puri D, Dhawan J, Mishra R K (2010). The paternal hidden agenda: Epigenetic inheritance through sperm chromatin. Epigenetics, 5(5): 386–391

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Roelfsema J H, Peters D J (2007). Rubinstein-Taybi syndrome: clinical and molecular overview. Expert Rev Mol Med, 9(23): 1–16

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pereira P M, Schneider A, Pannetier S, Heron D, Hanauer A (2010). Coffin-Lowry syndrome. Eur J Hum Genet, 18(6): 627–633

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu H, Liu X, Deng Y, Qing H (2013). DNA methylation, a hand behind neurodegenerative diseases. Front Aging Neurosci, 5: 85

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang S C, Oelze B, Schumacher A (2008). Age-specific epigenetic drift in late-onset Alzheimer’s disease. PLoS One, 3(7): e2698

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The work is supported by grants from NSFC (31371059), NSFC (31671104), and Beijing Municipal Science & Technology Commission (Z161100000216126) to J.-S.G. J.-S.G. is supported by Beijing Nova program (2015B057).

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Guan, JS., Xie, H. & Liu, SX. Epigenetic regulators sculpt the plastic brain. Front. Biol. 12, 317–332 (2017). https://doi.org/10.1007/s11515-017-1465-z

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