1932

Abstract

In this review, we discuss the potential pharmacological targeting of a set of powerful epigenetic mechanisms: DNA methylation control systems in the central nervous system (CNS). Specifically, we focus on the possible use of these targets for novel future treatments for learning and memory disorders. We first describe several unique pharmacological attributes of epigenetic mechanisms, especially DNA cytosine methylation, as potential drug targets. We then present an overview of the existing literature regarding DNA methylation control pathways and enzymes in the nervous system, particularly as related to synaptic function, plasticity, learning and memory. Lastly, we speculate upon potential categories of CNS cognitive disorders that might be amenable to methylomic targeting.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-010814-124527
2015-01-06
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/55/1/annurev-pharmtox-010814-124527.html?itemId=/content/journals/10.1146/annurev-pharmtox-010814-124527&mimeType=html&fmt=ahah

Literature Cited

  1. Cedar H, Bergman Y. 1.  2009. Linking DNA methylation and histone modification: patterns and paradigms. Nat. Rev. Genet. 10:295–304 [Google Scholar]
  2. Day JJ, Sweatt JD. 2.  2010. DNA methylation and memory formation. Nat. Neurosci. 13:1319–23 [Google Scholar]
  3. Day JJ, Sweatt JD. 3.  2011. Epigenetic mechanisms in cognition. Neuron 70:813–29 [Google Scholar]
  4. Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM. 4.  et al. 1999. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat. Genet. 23:58–61 [Google Scholar]
  5. Kass SU, Landsberger N, Wolffe AP. 5.  1997. DNA methylation directs a time-dependent repression of transcription initiation. Curr. Biol. 7:157–65 [Google Scholar]
  6. Fujita N, Watanabe S, Ichimura T, Ohkuma Y, Chiba T. 6.  et al. 2003. MCAF mediates MBD1-dependent transcriptional repression. Mol. Cell. Biol. 23:2834–43 [Google Scholar]
  7. Watt F, Molloy PL. 7.  1988. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev. 2:1136–43 [Google Scholar]
  8. Zheng Y, Josefowicz S, Chaudhry A, Peng XP, Forbush K, Rudensky AY. 8.  2010. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463:808–12 [Google Scholar]
  9. Miranda TB, Jones PA. 9.  2007. DNA methylation: the nuts and bolts of repression. J. Cell. Physiol. 213:384–90 [Google Scholar]
  10. Wu H, Coskun V, Tao J, Xie W, Ge W. 10.  et al. 2010. Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes. Science 329:444–48 [Google Scholar]
  11. Bell AC, Felsenfeld G. 11.  2000. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405:482–85 [Google Scholar]
  12. Pastor WA, Aravind L, Rao A. 12.  2013. TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat. Rev. Mol. Cell Biol. 14:341–56 [Google Scholar]
  13. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H. 13.  et al. 2009. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–35 [Google Scholar]
  14. Ito S, Shen L, Dai Q, Wu SC, Collins LB. 14.  et al. 2011. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300–3 [Google Scholar]
  15. Song CX, Szulwach KE, Dai Q, Fu Y, Mao SQ. 15.  et al. 2013. Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming. Cell 153:678–91 [Google Scholar]
  16. Hata K, Okano M, Lei H, Li E. 16.  2002. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129:1983–93 [Google Scholar]
  17. Yokomine T, Hata K, Tsudzuki M, Sasaki H. 17.  2006. Evolution of the vertebrate DNMT3 gene family: a possible link between existence of DNMT3L and genomic imprinting. Cytogenet. Genome Res. 113:75–80 [Google Scholar]
  18. Arand J, Spieler D, Karius T, Branco MR, Meilinger D. 18.  et al. 2012. In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases. PLOS Genet. 8:e1002750 [Google Scholar]
  19. Song J, Teplova M, Ishibe-Murakami S, Patel DJ. 19.  2012. Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science 335:709–12 [Google Scholar]
  20. Ho KL, McNae IW, Schmiedeberg L, Klose RJ, Bird AP, Walkinshaw MD. 20.  2008. MeCP2 binding to DNA depends upon hydration at methyl-CpG. Mol. Cell 29:525–31 [Google Scholar]
  21. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. 21.  1999. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23:185–88 [Google Scholar]
  22. Couvert PB, Aquaviva T, Poirier C, Moraine K, Gendrot C. 22.  et al. 2001. MECP2 is highly mutated in X-linked mental retardation. Hum. Mol. Genet. 10:941–46 [Google Scholar]
  23. Gommers-Ampt JH, Van Leeuwen F, de Beer ALJ, Vliegenthart JF, Dizdaroglu M. 23.  et al. 1993. β-d-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei. Cell 75:1129–36 [Google Scholar]
  24. Iyer LM, Anantharaman V, Wolf MY, Aravind L. 24.  2008. Comparative genomics of transcription factors and chromatin proteins in parasitic protists and other eukaryotes. Int. J. Parasitol. 38:1–31 [Google Scholar]
  25. Iyer LM, Tahiliani M, Rao A, Aravind L. 25.  2009. Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids. Cell Cycle 8:1698–710 [Google Scholar]
  26. Hu L, Li Z, Cheng J, Rao Q, Gong W. 26.  et al. 2013. Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation. Cell 155:1545–55 [Google Scholar]
  27. Ma DK, Marchetto MC, Guo JU, Ming GL, Gage FH, Song H. 27.  2010. Epigenetic choreographers of neurogenesis in the adult mammalian brain. Nat. Neurosci. 13:1338–44 [Google Scholar]
  28. Feng J, Fouse S, Fan G. 28.  2007. Epigenetic regulation of neural gene expression and neuronal function. Pediatric. Res. 61:58R–63R [Google Scholar]
  29. Meaney MJ, Ferguson-Smith AC. 29.  2010. Epigenetic regulation of the neural transcriptome: the meaning of the marks. Nat. Neurosci. 13:1313–18 [Google Scholar]
  30. Akbarian S, Beeri MS, Haroutunian V. 30.  2013. Epigenetic determinants of healthy and diseased brain aging and cognition. JAMA Neurol. 70:711–18 [Google Scholar]
  31. Zovkic IB, Guzman-Karlsson MC, Sweatt JD. 31.  2013. Epigenetic regulation of memory formation and maintenance. Learn. Mem. 20:61–74 [Google Scholar]
  32. Guo JU, Ma DK, Mo H, Ball MP, Jang MH. 32.  et al. 2011. Neuronal activity modifies the DNA methylation landscape in the adult brain. Nat. Neurosci. 14:1345–51 [Google Scholar]
  33. Day JJ, Childs D, Guzman-Karlsson MC, Kibe M, Moulden J. 33.  et al. 2013. DNA methylation regulates associative reward learning. Nat. Neurosci. 16:1445–52 [Google Scholar]
  34. Miller CA, Gavin CF, White JA, Parrish RR, Honasoge A. 34.  et al. 2010. Cortical DNA methylation maintains remote memory. Nat. Neurosci. 13:664–66 [Google Scholar]
  35. Miller CA, Sweatt JD. 35.  2007. Covalent modification of DNA regulates memory formation. Neuron 53:857–69 [Google Scholar]
  36. Roth TL, Lubin FD, Funk AJ, Sweatt JD. 36.  2009. Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol. Psychiatry 65:760–69 [Google Scholar]
  37. Weaver IC, Cervoni N, Champagne FA, D'Alessio AC, Sharma S. 37.  et al. 2004. Epigenetic programming by maternal behavior. Nat. Neurosci. 7:847–54 [Google Scholar]
  38. Monsey MS, Ota KT, Akingbade IF, Hong ES, Schafe GE. 38.  2011. Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. PLOS ONE 6:e19958 [Google Scholar]
  39. Levenson JM, Roth TL, Lubin FD, Miller CA, Huang IC. 39.  et al. 2006. Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J. Biol. Chem. 281:15763–73 [Google Scholar]
  40. Rudenko A, Dawlaty MM, Seo J, Cheng AW, Meng J. 40.  et al. 2013. Tet1 is critical for neuronal activity-regulated gene expression and memory extinction. Neuron 79:1109–22 [Google Scholar]
  41. Kaas GA, Zhong C, Eason DE, Ross DL, Vachhani RV. 41.  et al. 2013. TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation. Neuron 79:1086–93 [Google Scholar]
  42. Zhang RR, Cui QY, Murai K, Lim YC, Smith ZD. 42.  et al. 2013. Tet1 regulates adult hippocampal neurogenesis and cognition. Cell Stem Cell 13:237–45 [Google Scholar]
  43. Vassoler FM, White SL, Schmidt HD, Sadri-Vakili G, Pierce RC. 43.  2013. Epigenetic inheritance of a cocaine-resistance phenotype. Nat. Neurosci. 16:42–47 [Google Scholar]
  44. Huang Y, Pastor WA, Shen Y, Tahiliani M, Liu DR, Rao A. 44.  2010. The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing. PLOS ONE 5:e8888 [Google Scholar]
  45. Yu M, Hon GC, Szulwach KE, Song CX, Jin P. 45.  et al. 2012. Tet-assisted bisulfite sequencing of 5-hydroxymethylcytosine. Nat. Prot. 7:2159–70 [Google Scholar]
  46. Yu M, Hon GC, Szulwach KE, Song CX, Zhang L. 46.  et al. 2012. Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome. Cell 149:1368–80 [Google Scholar]
  47. Kriaucionis S, Heintz N. 47.  2009. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929–30 [Google Scholar]
  48. Guo JU, Su Y, Shin JH, Shin J, Li H. 48.  et al. 2014. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat. Neurosci. 17:215–22 [Google Scholar]
  49. Lister R, Ecker JR. 49.  2009. Finding the fifth base: genome-wide sequencing of cytosine methylation. Genome Res. 19:959–66 [Google Scholar]
  50. Lister R, Gregory BD, Ecker JR. 50.  2009. Next is now: new technologies for sequencing of genomes, transcriptomes, and beyond. Curr. Opin. Plant Biol. 12:107–18 [Google Scholar]
  51. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA. 51.  et al. 2013. Global epigenomic reconfiguration during mammalian brain development. Science 341:6146 [Google Scholar]
  52. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G. 52.  et al. 2009. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315–22 [Google Scholar]
  53. Harris RA, Wang T, Coarfa C, Nagarajan RP, Hong C. 53.  et al. 2010. Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications. Nat. Biotechnol. 28:1097–105 [Google Scholar]
  54. Bock C, Tomazou EM, Brinkman AB, Muller F, Simmer F. 54.  et al. 2010. Quantitative comparison of genome-wide DNA methylation mapping technologies. Nat. Biotechnol. 28:1106–14 [Google Scholar]
  55. Bock C. 55.  2012. Analysing and interpreting DNA methylation data. Nat. Rev. Genet. 13:705–19 [Google Scholar]
  56. Consortium EP, Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R. 56.  et al. 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816 [Google Scholar]
  57. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T. 57.  et al. 2009. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–93 [Google Scholar]
  58. Dulac C. 58.  2010. Brain function and chromatin plasticity. Nature 465:728–35 [Google Scholar]
  59. Suzuki MM, Bird A. 59.  2008. DNA methylation landscapes: provocative insights from epigenomics. Nat. Rev. Genet. 9:465–76 [Google Scholar]
  60. Klose RJ, Bird AP. 60.  2006. Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 31:89–97 [Google Scholar]
  61. Holliday R. 61.  2006. Epigenetics: a historical overview. Epigenetics 1:76–80 [Google Scholar]
  62. Guo JU, Su Y, Zhong C, Ming GL, Song H. 62.  2011. Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond. Cell Cycle 10:2662–68 [Google Scholar]
  63. Guo JU, Su Y, Zhong C, Ming GL, Song H. 63.  2011. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145:423–34 [Google Scholar]
  64. Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE. 64.  et al. 2013. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 23:555–67 [Google Scholar]
  65. Xie W, Barr CL, Kim A, Yue F, Lee AY. 65.  et al. 2012. Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Cell 148:816–31 [Google Scholar]
  66. Ziller MJ, Muller F, Liao J, Zhang Y, Gu H. 66.  et al. 2011. Genomic distribution and inter-sample variation of non-CpG methylation across human cell types. PLOS Genet. 7:e1002389 [Google Scholar]
  67. Feng J, Zhou Y, Campbell SL, Le T, Li E. 67.  et al. 2010. Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat. Neurosci. 13:423–30 [Google Scholar]
  68. Gräff J, Tsai L-H. 68.  2013. Histone acetylation: molecular mnemonics on the chromatin. Nat. Rev. Neurosci. 14:97–111 [Google Scholar]
  69. Gräff J, Tsai L-H. 69.  2013. The potential of HDAC inhibitors as cognitive enhancers. Annu. Rev. Pharmacol. Toxicol. 53:311–30 [Google Scholar]
  70. Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML. 70.  et al. 2009. Neuronal activity–induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074–77 [Google Scholar]
  71. LaPlant Q, Vialou V, Covington HE III, Dumitriu D, Feng J. 71.  et al. 2010. Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat. Neurosci. 13:1137–43 [Google Scholar]
  72. Maddox SA, Schafe GE. 72.  2011. Epigenetic alterations in the lateral amygdala are required for reconsolidation of a Pavlovian fear memory. Learn. Mem. 18:579–93 [Google Scholar]
  73. Weaver IC, Champagne FA, Brown SE, Dymov S, Sharma S. 73.  et al. 2005. Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J. Neurosci. 25:11045–54 [Google Scholar]
  74. Dias BG, Ressler KJ. 74.  2014. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat. Neurosci. 17:89–96 [Google Scholar]
  75. Rogerson T, Cai DJ, Frank A, Sano Y, Shobe J. 75.  et al. 2014. Synaptic tagging during memory allocation. Nat. Rev. Neurosci. 15:157–69 [Google Scholar]
  76. Frankland PW, Bontempi B. 76.  2005. The organization of recent and remote memories. Nat. Rev. Neurosci. 6:119–30 [Google Scholar]
  77. Flavell SW, Greenberg ME. 77.  2008. Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system. Annu. Rev. Neurosci. 31:563–90 [Google Scholar]
  78. Jüttermann R, Li E, Jaenisch R. 78.  1994. Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc. Natl. Acad. Sci. USA 91:11797–801 [Google Scholar]
  79. Okano M, Bell DW, Haber DA, Li E. 79.  1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–57 [Google Scholar]
  80. Oliveira AMM, Hemstedt TJ, Bading H. 80.  2012. Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities. Nat. Neurosci. 15:1111–13 [Google Scholar]
  81. Sultan FA, Sweatt JD. 81.  2013. The role of the gadd45 family in the nervous system: a focus on neurodevelopment, neuronal injury, and cognitive neuroepigenetics. Adv. Exp. Med. Biol. 793:81–119 [Google Scholar]
  82. Bennett CF, Swayze EE. 82.  2010. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol. 50:259–93 [Google Scholar]
  83. Southwell AL, Skotte NH, Bennett CF, Hayden MR. 83.  2012. Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases. Trends Mol. Med. 18:634–43 [Google Scholar]
  84. Kordasiewicz HB, Stanek LM, Wancewicz EV, Mazur C, McAlonis MM. 84.  et al. 2012. Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis. Neuron 74:1031–44 [Google Scholar]
  85. Mirkin CA, Letsinger RL, Mucic RC, Storhoff JJ. 85.  1996. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382:607–9 [Google Scholar]
  86. Rosi NL, Giljohann DA, Thaxton CS, Lytton-Jean AK, Han MS, Mirkin CA. 86.  2006. Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312:1027–30 [Google Scholar]
  87. Jensen SA, Day ES, Ko CH, Hurley LA, Luciano JP. 87.  et al. 2013. Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci. Transl. Med. 5:209ra152 [Google Scholar]
  88. Zhang K, Hao L, Hurst SJ, Mirkin CA. 88.  2012. Antibody-linked spherical nucleic acids for cellular targeting. J. Am. Chem. Soc. 134:16488–91 [Google Scholar]
  89. Hsu PD, Zhang F. 89.  2012. Dissecting neural function using targeted genome engineering technologies. ACS Chem. Neurosci. 3:603–10 [Google Scholar]
  90. Cong L, Zhou R, Kuo YC, Cunniff M, Zhang F. 90.  2012. Comprehensive interrogation of natural TALE DNA-binding modules and transcriptional repressor domains. Nat. Commun. 3:968 [Google Scholar]
  91. Briggs AW, Rios X, Chari R, Yang L, Zhang F. 91.  et al. 2012. Iterative capped assembly: rapid and scalable synthesis of repeat-module DNA such as TAL effectors from individual monomers. Nucleic Acids Res. 40:e117 [Google Scholar]
  92. Sanjana NE, Cong L, Zhou Y, Cunniff MM, Feng G, Zhang F. 92.  2012. A transcription activator-like effector toolbox for genome engineering. Nat. Protoc. 7:171–92 [Google Scholar]
  93. Konermann S, Brigham MD, Trevino AE, Hsu PD, Heidenreich M. 93.  et al. 2013. Optical control of mammalian endogenous transcription and epigenetic states. Nature 500:472–76 [Google Scholar]
  94. Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM. 94.  et al. 2013. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nat. Biotechnol. 31:1137–42 [Google Scholar]
  95. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 95.  2012. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–21 [Google Scholar]
  96. Mali P, Yang L, Esvelt KM, Aach J, Guell M. 96.  et al. 2013. RNA-guided human genome engineering via Cas9. Science 339:823–26 [Google Scholar]
  97. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA. 97.  et al. 2014. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343:84–87 [Google Scholar]
  98. Larson MH, Gilbert LA, Wang X, Lim WA, Weissman JS, Qi LS. 98.  2013. CRISPR interference (CRISPRi) for sequence-specific control of gene expression. Nat. Protoc. 8:2180–96 [Google Scholar]
  99. Jennings JH, Stuber GD. 99.  2014. Tools for resolving functional activity and connectivity within intact neural circuits. Curr. Biol. 24:R41–50 [Google Scholar]
  100. Jennings JH, Rizzi G, Stamatakis AM, Ung RL, Stuber GD. 100.  2013. The inhibitory circuit architecture of the lateral hypothalamus orchestrates feeding. Science 341:1517–21 [Google Scholar]
  101. Graca I, Sousa E, Baptista T, Almeida M, Ramalho-Carvalho J. 101.  et al. 2013. Anti-tumoral effect of the non-nucleoside DNMT inhibitor RG108 in human prostate cancer cells. Curr. Pharma. Des. 20:1803–11 [Google Scholar]
  102. Robert MF, Morin S, Beaulieu N, Gauthier F, Chute IC. 102.  et al. 2003. DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat. Genet. 33:61–65 [Google Scholar]
  103. Lyko F, Brown R. 103.  2005. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J. Natl. Cancer Inst. 97:1498–506 [Google Scholar]
  104. Yang PM, Lin YT, Shun CT, Lin SH, Wei TT. 104.  et al. 2013. Zebularine inhibits tumorigenesis and stemness of colorectal cancer via p53-dependent endoplasmic reticulum stress. Sci. Rep. 3:3219 [Google Scholar]
  105. Huang HS, Allen JA, Mabb AM, King IF, Miriyala J. 105.  et al. 2012. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 481:185–89 [Google Scholar]
  106. Yu D, Pendergraff H, Liu J, Kordasiewicz HB, Cleveland DW. 106.  et al. 2012. Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression. Cell 150:895–908 [Google Scholar]
  107. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST. 107.  et al. 2008. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320:1224–29 [Google Scholar]
  108. Sweatt JD. 108.  2013. Pitt-Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription. Exp. Mol. Med. 45:e21 [Google Scholar]
  109. Blake DJ, Forrest M, Chapman RM, Tinsley CL, O'Donovan MC, Owen MJ. 109.  2010. TCF4, schizophrenia, and Pitt-Hopkins Syndrome. Schizophr. Bull. 36:443–47 [Google Scholar]
  110. Graff J, Joseph NF, Horn ME, Samiei A, Meng J. 110.  et al. 2014. Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories. Cell 156:261–76 [Google Scholar]
  111. 111. Nature 2014. Suicide watch. Nature 506:131 [Google Scholar]
  112. Na KS, Chang HS, Won E, Han KM, Choi S. 112.  et al. 2014. Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder. PLOS ONE 9:e85425 [Google Scholar]
  113. Kang HJ, Kim JM, Lee JY, Kim SY, Bae KY. 113.  et al. 2013. BDNF promoter methylation and suicidal behavior in depressive patients. J. Affect. Disord. 151:679–85 [Google Scholar]
  114. Grayson DR, Chen Y, Costa E, Dong E, Guidotti A. 114.  et al. 2006. The human reelin gene: transcription factors (+), repressors (−) and the methylation switch (+/−) in schizophrenia. Pharmacol. Ther. 111:272–86 [Google Scholar]
  115. Grayson DR, Jia X, Chen Y, Sharma RP, Mitchell CP. 115.  et al. 2005. Reelin promoter hypermethylation in schizophrenia. Proc. Natl. Acad. Sci. USA 102:9341–46 [Google Scholar]
  116. Huang HS, Akbarian S. 116.  2007. GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia. PLOS ONE 2:e809 [Google Scholar]
  117. Kundakovic M, Chen Y, Guidotti A, Grayson DR. 117.  2009. The reelin and GAD67 promoters are activated by epigenetic drugs that facilitate the disruption of local repressor complexes. Mol. Pharmacol. 75:342–54 [Google Scholar]
  118. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F. 118.  et al. 1992. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc. Natl. Acad. Sci. USA 89:1827–31 [Google Scholar]
  119. Sutcliffe JS, Nelson DL, Zhang F, Pieretti M, Caskey CT. 119.  et al. 1992. DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum. Mol. Genet. 1:397–400 [Google Scholar]
  120. Coppieters N, Dieriks BV, Lill C, Faull RLM, Curtis MA, Dragunow M. 120.  2013. Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain. Neurobiol. Aging 35:1334–44 [Google Scholar]
  121. Sanchez-Mut JV, Aso E, Panayotis N, Lott I, Dierssen M. 121.  et al. 2013. DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease. Brain: J. Neurol. 136:3018–27 [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-010814-124527
Loading
/content/journals/10.1146/annurev-pharmtox-010814-124527
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error