Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies

Holliday, 1987, DNA methylation and epigenetic defects in carcinogenesis, Mutat Res, 181, 215, 10.1016/0027-5107(87)90098-4 Feinberg, 2007, Phenotypic plasticity and the epigenetics of human disease, Nature, 447, 433, 10.1038/nature05919 Fraga, 2005, Epigenetic differences arise during the lifetime of monozygotic twins, Proc Natl Acad Sci USA, 102, 10604, 10.1073/pnas.0500398102 Esteller, 2007, Rett syndrome: the first forty years: 1966–2006, Epigenetics, 2, 1, 10.4161/epi.2.1.3695 Amir, 1999, Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2, Nat Genet, 23, 185, 10.1038/13810 Bird, 2002, DNA methylation patterns and epigenetic memory, Genes Dev, 16, 6, 10.1101/gad.947102 Esteller, 2008, Epigenetics in evolution and disease, Lancet, 372, S90, 10.1016/S0140-6736(08)61887-5 Reik, 2001, Epigenetic reprogramming in mammalian development, Science, 293, 1089, 10.1126/science.1063443 Edwards, 2008, Environmental exposures and gene regulation in disease etiology, Cien Saude Colet, 13, 269, 10.1590/S1413-81232008000100030 Edwards, 2007, Mechanisms regulating imprinted genes in clusters, Curr Opin Cell Biol, 19, 281, 10.1016/j.ceb.2007.04.013 Bestor, 2000, The DNA methyltransferases of mammals, Hum Mol Genet, 9, 2395, 10.1093/hmg/9.16.2395 Fatemi, 2006, MBD family proteins: reading the epigenetic code, J Cell Sci, 119, 3033, 10.1242/jcs.03099 Lopez-Serra, 2008, Proteins that bind methylated DNA and human cancer: reading the wrong words, Br J Cancer, 98, 1881, 10.1038/sj.bjc.6604374 Al-Mahdawi, 2008, The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues, Hum Mol Genet, 17, 735, 10.1093/hmg/ddm346 Hauke, 2009, Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition, Hum Mol Genet, 18, 304, 10.1093/hmg/ddn357 Moscarello, 2007, The role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis, Neurochem Res, 32, 251, 10.1007/s11064-006-9144-5 Esteller, 2007, Cancer epigenomics: DNA methylomes and histone-modification maps, Nat Rev Genet, 8, 286, 10.1038/nrg2005 Esteller, 2000, Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents, N Engl J Med, 343, 1350, 10.1056/NEJM200011093431901 Hegi, 2005, MGMT gene silencing and benefit from temozolomide in glioblastoma, N Engl J Med, 352, 997, 10.1056/NEJMoa043331 Paz, 2004, CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas, Clin Cancer Res, 10, 4933, 10.1158/1078-0432.CCR-04-0392 Kouzarides, 2007, Chromatin modifications and their function, Cell, 128, 693, 10.1016/j.cell.2007.02.005 Bernstein, 2007, The mammalian epigenome, Cell, 128, 669, 10.1016/j.cell.2007.01.033 Agger, 2008, The emerging functions of histone demethylases, Curr Opin Genet Dev, 18, 159, 10.1016/j.gde.2007.12.003 Camelo, 2005, Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis, J Neuroimmunol, 164, 10, 10.1016/j.jneuroim.2005.02.022 Gondcaille, 2005, Phenylbutyrate up-regulates the adrenoleukodystrophy-related gene as a nonclassical peroxisome proliferator, J Cell Biol, 169, 93, 10.1083/jcb.200501036 Rai, 2008, HDAC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model, PLoS One, 3, e1958, 10.1371/journal.pone.0001958 Soragni, 2008, Long intronic GAA*TTC repeats induce epigenetic changes and reporter gene silencing in a molecular model of Friedreich ataxia, Nucleic Acids Res, 36, 6056, 10.1093/nar/gkn604 Gao, 2008, Posttranscriptional control of neuronal development by microRNA networks, Trends Neurosci, 31, 20, 10.1016/j.tins.2007.10.004 Mehler, 2008, Epigenetic principles and mechanisms underlying nervous system functions in health and disease, Prog Neurobiol, 86, 305, 10.1016/j.pneurobio.2008.10.001 Jones, 2007, The epigenomics of cancer, Cell, 128, 683, 10.1016/j.cell.2007.01.029 Esteller, 2008, Epigenetics in cancer, N Engl J Med, 358, 1148, 10.1056/NEJMra072067 Esteller, 2003, Relevance of DNA methylation in the management of cancer, Lancet Oncol, 4, 351, 10.1016/S1470-2045(03)01115-X Feinberg, 1983, Hypomethylation distinguishes genes of some human cancers from their normal counterparts, Nature, 301, 89, 10.1038/301089a0 Costello, 2000, Aberrant CpG-island methylation has non-random and tumour-type-specific patterns, Nat Genet, 24, 132, 10.1038/72785 Esteller, 2001, A gene hypermethylation profile of human cancer, Cancer Res, 61, 3225 Martinez, 2009, A microarray-based DNA methylation study of glioblastoma multiforme, Epigenetics, 4, 255, 10.4161/epi.9130 2008, Comprehensive genomic characterization defines human glioblastoma genes and core pathways, Nature, 455, 1061, 10.1038/nature07385 Alaminos, 2004, Clustering of gene hypermethylation associated with clinical risk groups in neuroblastoma, J Natl Cancer Inst, 96, 1208, 10.1093/jnci/djh224 Fraga, 2005, Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer, Nat Genet, 37, 391, 10.1038/ng1531 Fraga, 2005, Towards the human cancer epigenome: a first draft of histone modifications, Cell Cycle, 4, 1377, 10.4161/cc.4.10.2113 Seligson, 2005, Global histone modification patterns predict risk of prostate cancer recurrence, Nature, 435, 1262, 10.1038/nature03672 Chahrour, 2007, The story of Rett syndrome: from clinic to neurobiology, Neuron, 56, 422, 10.1016/j.neuron.2007.10.001 del Gaudio, 2006, Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males, Genet Med, 8, 784, 10.1097/01.gim.0000250502.28516.3c Collins, 2004, Mild overexpression of MeCP2 causes a progressive neurological disorder in mice, Hum Mol Genet, 13, 2679, 10.1093/hmg/ddh282 Ballestar, 2005, The impact of MECP2 mutations in the expression patterns of Rett syndrome patients, Hum Genet, 116, 91, 10.1007/s00439-004-1200-0 Chen, 2001, Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice, Nat Genet, 27, 327, 10.1038/85906 Ballas, 2009, Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology, Nat Neurosci, 12, 311, 10.1038/nn.2275 Maezawa, 2009, Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions, J Neurosci, 29, 5051, 10.1523/JNEUROSCI.0324-09.2009 Tudor, 2002, Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain, Proc Natl Acad Sci USA, 99, 15536, 10.1073/pnas.242566899 Urdinguio, 2008, Mecp2-null mice provide new neuronal targets for Rett syndrome, PLoS ONE, 3, e3669, 10.1371/journal.pone.0003669 Urdinguio, 2007, Histone H3 and H4 modification profiles in a Rett syndrome mouse model, Epigenetics, 2, 11, 10.4161/epi.2.1.3698 Guy, 2007, Reversal of neurological defects in a mouse model of Rett syndrome, Science, 315, 1143, 10.1126/science.1138389 Tropea, 2009, Partial reversal of Rett syndrome-like symptoms in MeCP2 mutant mice, Proc Natl Acad Sci USA, 106, 2029, 10.1073/pnas.0812394106 Tao, 2004, Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation, Am J Hum Genet, 75, 1149, 10.1086/426460 Weaving, 2004, Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation, Am J Hum Genet, 75, 1079, 10.1086/426462 Mari, 2005, CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome, Hum Mol Genet, 14, 1935, 10.1093/hmg/ddi198 Jones, 1998, Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription, Nat Genet, 19, 187, 10.1038/561 Nan, 1998, Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex, Nature, 393, 386, 10.1038/30764 Chahrour, 2008, MeCP2, a key contributor to neurological disease, activates and represses transcription, Science, 320, 1224, 10.1126/science.1153252 Yasui, 2007, Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes, Proc Natl Acad Sci USA, 104, 19416, 10.1073/pnas.0707442104 Stevens, 1990, Growth in the Rubinstein-Taybi syndrome, Am J Med Genet Suppl, 6, 51 Rubinstein, 1963, Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome, Am J Dis Child, 105, 588, 10.1001/archpedi.1963.02080040590010 Cantani, 1998, Rubinstein-Taybi syndrome. Review of 732 cases and analysis of the typical traits, Eur Rev Med Pharmacol Sci, 2, 81 Hennekam, 2006, Rubinstein-Taybi syndrome, Eur J Hum Genet, 14, 981, 10.1038/sj.ejhg.5201594 Hallam, 2006, Rubinstein-Taybi syndrome: molecular findings and therapeutic approaches to improve cognitive dysfunction, Cell Mol Life Sci, 63, 1725, 10.1007/s00018-005-5555-8 Bartsch, 2005, DNA sequencing of CREBBP demonstrates mutations in 56% of patients with Rubinstein-Taybi syndrome (RSTS) and in another patient with incomplete RSTS, Hum Genet, 117, 485, 10.1007/s00439-005-1331-y Roelfsema, 2005, Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease, Am J Hum Genet, 76, 572, 10.1086/429130 Petrij, 1995, Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP, Nature, 376, 348, 10.1038/376348a0 Schorry, 2008, Genotype-phenotype correlations in Rubinstein-Taybi syndrome, Am J Med Genet A, 146A, 2512, 10.1002/ajmg.a.32424 Chrivia, 1993, Phosphorylated CREB binds specifically to the nuclear protein CBP, Nature, 365, 855, 10.1038/365855a0 Bannister, 1996, The CBP co-activator is a histone acetyltransferase, Nature, 384, 641, 10.1038/384641a0 Kalkhoven, 2004, CBP and p300: HATs for different occasions, Biochem Pharmacol, 68, 1145, 10.1016/j.bcp.2004.03.045 Wood, 2005, Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage, Learn Mem, 12, 111, 10.1101/lm.86605 Lee, 2008, Monoallele deletion of CBP leads to pericentromeric heterochromatin condensation through ESET expression and histone H3 (K9) methylation, Hum Mol Genet, 17, 1774, 10.1093/hmg/ddn067 Young, 1988, The Coffin-Lowry syndrome, J Med Genet, 25, 344, 10.1136/jmg.25.5.344 Hanauer, 2002, Coffin-Lowry syndrome: clinical and molecular features, J Med Genet, 39, 705, 10.1136/jmg.39.10.705 Touraine, 2002, A syndromic form of X-linked mental retardation: the Coffin-Lowry syndrome, Eur J Pediatr, 161, 179, 10.1007/s00431-001-0904-6 Trivier, 1996, Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome, Nature, 384, 567, 10.1038/384567a0 Field, 2006, Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation, Clin Genet, 70, 509, 10.1111/j.1399-0004.2006.00723.x Pearson, 2001, Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions, Endocr Rev, 22, 153 Schaeffer, 1999, Mitogen-activated protein kinases: specific messages from ubiquitous messengers, Mol Cell Biol, 19, 2435, 10.1128/MCB.19.4.2435 De Cesare, 1998, Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene, Proc Natl Acad Sci USA, 95, 12202, 10.1073/pnas.95.21.12202 Merienne, 2001, Mitogen-regulated RSK2-CBP interaction controls their kinase and acetylase activities, Mol Cell Biol, 21, 7089, 10.1128/MCB.21.20.7089-7096.2001 Cho, 2005, The p53 protein is a novel substrate of ribosomal S6 kinase 2 and a critical intermediary for ribosomal S6 kinase 2 and histone H3 interaction, Cancer Res, 65, 3596, 10.1158/0008-5472.CAN-04-3935 Clayton, 2000, Phosphoacetylation of histone H3 on c-fos- and c-jun-associated nucleosomes upon gene activation, EMBO J, 19, 3714, 10.1093/emboj/19.14.3714 Gibbons, 1995, Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X), Am J Med Genet, 55, 288, 10.1002/ajmg.1320550309 Gibbons, 2006, Alpha thalassaemia-mental retardation, X linked, Orphanet J Rare Dis, 1, 15, 10.1186/1750-1172-1-15 Gibbons, 1992, X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis, Am J Hum Genet, 51, 1136 Gibbons, 2008, Mutations in the chromatin-associated protein ATRX, Hum Mutat, 29, 796, 10.1002/humu.20734 Gibbons, 1995, Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome), Cell, 80, 837, 10.1016/0092-8674(95)90287-2 Eisen, 1995, Evolution of the SNF2 family of proteins: subfamilies with distinct sequences and functions, Nucleic Acids Res, 23, 2715, 10.1093/nar/23.14.2715 Xue, 2003, The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies, Proc Natl Acad Sci USA, 100, 10635, 10.1073/pnas.1937626100 Baker, 2008, PHD fingers in human diseases: disorders arising from misinterpreting epigenetic marks, Mutat Res, 647, 3, 10.1016/j.mrfmmm.2008.07.004 Gibbons, 2000, Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation, Nat Genet, 24, 368, 10.1038/74191 Garrick, 2006, Loss of Atrx affects trophoblast development and the pattern of X-inactivation in extraembryonic tissues, PLoS Genet, 2, e58, 10.1371/journal.pgen.0020058 Argentaro, 2007, Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX, Proc Natl Acad Sci USA, 104, 11939, 10.1073/pnas.0704057104 McDowell, 1999, Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes, Proc Natl Acad Sci USA, 96, 13983, 10.1073/pnas.96.24.13983 Le Douarin, 1996, A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors, EMBO J, 15, 6701, 10.1002/j.1460-2075.1996.tb01060.x Berube, 2000, Cell cycle-dependent phosphorylation of the ATRX protein correlates with changes in nuclear matrix and chromatin association, Hum Mol Genet, 9, 539, 10.1093/hmg/9.4.539 Baumann, 2008, Association of ATRX with pericentric heterochromatin and the Y chromosome of neonatal mouse spermatogonia, BMC Mol Biol, 9, 29, 10.1186/1471-2199-9-29 De La Fuente, 2004, ATRX, a member of the SNF2 family of helicase/ATPases, is required for chromosome alignment and meiotic spindle organization in metaphase II stage mouse oocytes, Dev Biol, 272, 1, 10.1016/j.ydbio.2003.12.012 Ritchie, 2008, Loss of ATRX leads to chromosome cohesion and congression defects, J Cell Biol, 180, 315, 10.1083/jcb.200706083 Baumann, 2009, ATRX marks the inactive X chromosome (Xi) in somatic cells and during imprinted X chromosome inactivation in trophoblast stem cells, Chromosoma, 118, 209, 10.1007/s00412-008-0189-x Cardoso, 1998, Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein, Hum Mol Genet, 7, 679, 10.1093/hmg/7.4.679 Nan, 2007, Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation, Proc Natl Acad Sci USA, 104, 2709, 10.1073/pnas.0608056104 Gunzburg, 2007, Structural basis for the recognition and cross-linking of amyloid fibrils by human apolipoprotein E, J Biol Chem, 282, 35831, 10.1074/jbc.M706425200 Iwata, 2000, Identification of the major Abeta1–42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition, Nat Med, 6, 143, 10.1038/72237 Chen, 2009, The epigenetic effects of amyloid-beta(1–40) on global DNA and neprilysin genes in murine cerebral endothelial cells, Biochem Biophys Res Commun, 378, 57, 10.1016/j.bbrc.2008.10.173 Belyaev, 2009, Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease, EMBO Rep, 10, 94, 10.1038/embor.2008.222 Yasojima, 2001, Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of beta-amyloid peptide, Neurosci Lett, 297, 97, 10.1016/S0304-3940(00)01675-X Hellstrom-Lindahl, 2008, Age-dependent decline of neprilysin in Alzheimer's disease and normal brain: inverse correlation with A beta levels, Neurobiol Aging, 29, 210, 10.1016/j.neurobiolaging.2006.10.010 Baek, 2002, Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein, Cell, 110, 55, 10.1016/S0092-8674(02)00809-7 Kim, 2004, Inhibition of histone deacetylation enhances the neurotoxicity induced by the C-terminal fragments of amyloid precursor protein, J Neurosci Res, 75, 117, 10.1002/jnr.10845 Stante, 2009, Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand breaks, Proc Natl Acad Sci USA, 106, 5093, 10.1073/pnas.0810869106 Myung, 2008, Evidence of DNA damage in Alzheimer disease: phosphorylation of histone H2AX in astrocytes, Age, 30, 209, 10.1007/s11357-008-9050-7 Guan, 2009, HDAC2 negatively regulates memory formation and synaptic plasticity, Nature, 459, 55, 10.1038/nature07925 Siegmund, 2007, DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons, PLoS ONE, 2, e895, 10.1371/journal.pone.0000895 Bulk, 2009, S100A2 induces metastasis in non-small cell lung cancer, Clin Cancer Res, 15, 22, 10.1158/1078-0432.CCR-08-0953 Druse, 2007, S100B-mediated protection against the pro-apoptotic effects of ethanol on fetal rhombencephalic neurons, Brain Res, 1150, 46, 10.1016/j.brainres.2007.02.092 Ito, 2007, Phosphorylation by extracellular signal-regulated kinase of a multidomain adaptor protein, vinexin, at synapses, J Neurochem, 100, 545, 10.1111/j.1471-4159.2006.04222.x Wang, 2008, Age-specific epigenetic drift in late-onset Alzheimer's disease, PLoS ONE, 3, e2698, 10.1371/journal.pone.0002698 Ladd-Acosta, 2007, DNA methylation signatures within the human brain, Am J Hum Genet, 81, 1304, 10.1086/524110 Kontopoulos, 2006, Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity, Hum Mol Genet, 15, 3012, 10.1093/hmg/ddl243 Outeiro, 2007, Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease, Science, 317, 516, 10.1126/science.1143780 Nicholas, 2008, Striatal histone modifications in models of levodopa-induced dyskinesia, J Neurochem, 106, 486, 10.1111/j.1471-4159.2008.05417.x Pieper, 2008, Different methylation of the TNF-alpha promoter in cortex and substantia nigra: Implications for selective neuronal vulnerability, Neurobiol Dis, 32, 521, 10.1016/j.nbd.2008.09.010 Mogi, 1996, Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease, Neurosci Lett, 211, 13, 10.1016/0304-3940(96)12706-3 Steffan, 2000, The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription, Proc Natl Acad Sci USA, 97, 6763, 10.1073/pnas.100110097 Ryu, 2006, ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington's disease, Proc Natl Acad Sci USA, 103, 19176, 10.1073/pnas.0606373103 Stack, 2007, Modulation of nucleosome dynamics in Huntington's disease, Hum Mol Genet, 16, 1164, 10.1093/hmg/ddm064 Sadri-Vakili, 2007, Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models, Hum Mol Genet, 16, 1293, 10.1093/hmg/ddm078 Casaccia-Bonnefil, 2008, Evaluating epigenetic landmarks in the brain of multiple sclerosis patients: a contribution to the current debate on disease pathogenesis, Prog Neurobiol, 86, 368 Chao, 2009, Epigenetics in multiple sclerosis susceptibility: difference in transgenerational risk localizes to the major histocompatibility complex, Hum Mol Genet, 18, 261, 10.1093/hmg/ddn353 Fukuchi, 2009, Valproic acid induces up- or down-regulation of gene expression responsible for the neuronal excitation and inhibition in rat cortical neurons through its epigenetic actions, Neurosci Res, 65, 35, 10.1016/j.neures.2009.05.002 Cudkowicz, 2009, Phase 2 study of sodium phenylbutyrate in ALS, Amyotroph Lateral Scler, 10, 99, 10.1080/17482960802320487 Feng, 2008, Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model, Neuroscience, 155, 567, 10.1016/j.neuroscience.2008.06.040 Oksenberg, 2008, The genetics of multiple sclerosis: SNPs to pathways to pathogenesis, Nat Rev Genet, 9, 516, 10.1038/nrg2395 Brynedal, 2007, HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis, PLoS One, 2, e664, 10.1371/journal.pone.0000664 Lundmark, 2007, Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis, Nat Genet, 39, 1108, 10.1038/ng2106 Zivadinov, 2007, HLA-DRB1*1501, -DQB1*0301, -DQB1*0302, -DQB1*0602, and -DQB1*0603 alleles are associated with more severe disease outcome on MRI in patients with multiple sclerosis, Int Rev Neurobiol, 79, 521, 10.1016/S0074-7742(07)79023-2 Haines, 1998, Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group, Hum Mol Genet, 7, 1229, 10.1093/hmg/7.8.1229 Dyment, 2005, Complex interactions among MHC haplotypes in multiple sclerosis: susceptibility and resistance, Hum Mol Genet, 14, 2019, 10.1093/hmg/ddi206 Hansen, 2005, Concordance for multiple sclerosis in Danish twins: an update of a nationwide study, Mult Scler, 11, 504, 10.1191/1352458505ms1220oa Hansen, 2005, Risk for multiple sclerosis in dizygotic and monozygotic twins, Mult Scler, 11, 500, 10.1191/1352458505ms1202oa Poser, 2006, The multiple sclerosis trait and the development of multiple sclerosis: genetic vulnerability and environmental effect, Clin Neurol Neurosurg, 108, 227, 10.1016/j.clineuro.2005.11.019 Willer, 2003, Twin concordance and sibling recurrence rates in multiple sclerosis, Proc Natl Acad Sci USA, 100, 12877, 10.1073/pnas.1932604100 Kantarci, 2006, Men transmit MS more often to their children vs women: the Carter effect, Neurology, 67, 305, 10.1212/01.wnl.0000225070.13682.11 Mastronardi, 2007, Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated, J Neurosci Res, 85, 2006, 10.1002/jnr.21329 Moscarello, 1986, The role of charge microheterogeneity of basic protein in the formation and maintenance of the multilayered structure of myelin: a possible role in multiple sclerosis, J Neurosci Res, 15, 87, 10.1002/jnr.490150109 Moscarello, 1994, Myelin in multiple sclerosis is developmentally immature, J Clin Invest, 94, 146, 10.1172/JCI117300 D'Souza, 2005, Autocatalytic cleavage of myelin basic protein: an alternative to molecular mimicry, Biochemistry, 44, 12905, 10.1021/bi051152f Musse, 2006, Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope, Proc Natl Acad Sci USA, 103, 4422, 10.1073/pnas.0509158103 Rudick, 2009, Current approaches to the identification and management of breakthrough disease in patients with multiple sclerosis, Lancet Neurol, 8, 545, 10.1016/S1474-4422(09)70082-1 Reid, 2009, Mechanisms of human inherited epilepsies, Prog Neurobiol, 87, 41, 10.1016/j.pneurobio.2008.09.016 Meunier, 1963, Pharmacodynamic properties of N-dipropylacetic acid, Therapie, 18, 435 Phiel, 2001, Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen, J Biol Chem, 276, 36734, 10.1074/jbc.M101287200 Sng, 2006, Histone modifications in kainate-induced status epilepticus, Eur J Neurosci, 23, 1269, 10.1111/j.1460-9568.2006.04641.x Huang, 2002, Altered histone acetylation at glutamate receptor 2 and brain-derived neurotrophic factor genes is an early event triggered by status epilepticus, J Neurosci, 22, 8422, 10.1523/JNEUROSCI.22-19-08422.2002 Tsankova, 2004, Histone modifications at gene promoter regions in rat hippocampus after acute and chronic electroconvulsive seizures, J Neurosci, 24, 5603, 10.1523/JNEUROSCI.0589-04.2004 Kwiatkowski, 2009, Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis, Science, 323, 1205, 10.1126/science.1166066 Neumann, 2006, Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis, Science, 314, 130, 10.1126/science.1134108 Simpson, 2009, Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration, Hum Mol Genet, 18, 472, 10.1093/hmg/ddn375 Pasinelli, 2004, Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria, Neuron, 43, 19, 10.1016/j.neuron.2004.06.021 Wang, 2008, Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription, Nature, 454, 126, 10.1038/nature06992 Han, 2008, Gcn5- and Elp3-induced histone H3 acetylation regulates hsp70 gene transcription in yeast, Biochem J, 409, 779, 10.1042/BJ20070578 Koyama, 2006, Alteration of familial ALS-linked mutant SOD1 solubility with disease progression: its modulation by the proteasome and Hsp70, Biochem Biophys Res Commun, 343, 719, 10.1016/j.bbrc.2006.02.170 Patel, 2005, Hsp27 and Hsp70 administered in combination have a potent protective effect against FALS-associated SOD1-mutant-induced cell death in mammalian neuronal cells, Brain Res Mol Brain Res, 134, 256, 10.1016/j.molbrainres.2004.10.028 Chang, 2001, Treatment of spinal muscular atrophy by sodium butyrate, Proc Natl Acad Sci USA, 98, 9808, 10.1073/pnas.171105098 Herman, 2006, Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia, Nat Chem Biol, 2, 551, 10.1038/nchembio815 Sugai, 2004, Benefit of valproic acid in suppressing disease progression of ALS model mice, Eur J Neurosci, 20, 3179, 10.1111/j.1460-9568.2004.03765.x Chiurazzi, 1998, In vitro reactivation of the FMR1 gene involved in fragile X syndrome, Hum Mol Genet, 7, 109, 10.1093/hmg/7.1.109 Alarcon, 2004, Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration, Neuron, 42, 947, 10.1016/j.neuron.2004.05.021 Korzus, 2004, CBP histone acetyltransferase activity is a critical component of memory consolidation, Neuron, 42, 961, 10.1016/j.neuron.2004.06.002 Vecsey, 2007, Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation, J Neurosci, 27, 6128, 10.1523/JNEUROSCI.0296-07.2007 Levenson, 2004, Regulation of histone acetylation during memory formation in the hippocampus, J Biol Chem, 279, 40545, 10.1074/jbc.M402229200 Yeh, 2004, Acetylation of nuclear factor-kappaB in rat amygdala improves long-term but not short-term retention of fear memory, Mol Pharmacol, 65, 1286, 10.1124/mol.65.5.1286 Hogarth, 2007, Sodium phenylbutyrate in Huntington's disease: a dose-finding study, Mov Disord, 22, 1962, 10.1002/mds.21632 Steffan, 2001, Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila, Nature, 413, 739, 10.1038/35099568 Dompierre, 2007, Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation, J Neurosci, 27, 3571, 10.1523/JNEUROSCI.0037-07.2007 Gardian, 2005, Neuroprotective effects of phenylbutyrate in the N171–82Q transgenic mouse model of Huntington's disease, J Biol Chem, 280, 556, 10.1074/jbc.M410210200 El-Amouri, 2008, Neprilysin: an enzyme candidate to slow the progression of Alzheimer's disease, Am J Pathol, 172, 1342, 10.2353/ajpath.2008.070620 Fischer, 2007, Recovery of learning and memory is associated with chromatin remodelling, Nature, 447, 178, 10.1038/nature05772 Youngson, 2008, Transgenerational epigenetic effects, Annu Rev Genomics Hum Genet, 9, 233, 10.1146/annurev.genom.9.081307.164445 Ashe, 2008, A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development, Genome Biol, 9, R182, 10.1186/gb-2008-9-12-r182