Epigenetic Mechanisms in Cognition

Although the critical role for epigenetic mechanisms in development and cell differentiation has long been appreciated, recent evidence reveals that these mechanisms are also employed in postmitotic neurons as a means of consolidating and stabilizing cognitive-behavioral memories. In this review, we discuss evidence for an "epigenetic code" in the central nervous system that mediates synaptic plasticity, learning, and memory. We consider how specific epigenetic changes are regulated and may interact with each other during memory formation and how these changes manifest functionally at the cellular and circuit levels. We also describe a central role for mitogen-activated protein kinases in controlling chromatin signaling in plasticity and memory. Finally, we consider how aberrant epigenetic modifications may lead to cognitive disorders that affect learning and memory, and we review the therapeutic potential of epigenetic treatments for the amelioration of these conditions.

[1]  C. Glass,et al.  Factor-specific modulation of CREB-binding protein acetyltransferase activity. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[2]  T. Carew,et al.  A comparison of the mechanistic relationships between development and learning in Aplysia. , 1994, Progress in brain research.

[3]  Paul Greengard,et al.  A phosphatase cascade by which rewarding stimuli control nucleosomal response , 2008, Nature.

[4]  Kerwin Lee IZlein.  The Language of History , 1997 .

[5]  R. Jaenisch,et al.  Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice , 2001, Nature Genetics.

[6]  J. Sweatt,et al.  The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory , 2001, Journal of neurochemistry.

[7]  Lan Ma,et al.  Chronic Cocaine-Induced H3 Acetylation and Transcriptional Activation of CaMKIIα in the Nucleus Accumbens Is Critical for Motivation for Drug Reinforcement , 2010, Neuropsychopharmacology.

[8]  B. Aragona,et al.  Opposing Regulation of Pair Bond Formation by cAMP Signaling within the Nucleus Accumbens Shell , 2007, The Journal of Neuroscience.

[9]  S. Luo,et al.  High-Resolution Analysis of Parent-of-Origin Allelic Expression in the Mouse Brain , 2010, Science.

[10]  E. Butelman,et al.  Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction , 2005, Nature Neuroscience.

[11]  I. Weaver,et al.  Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life , 2005, The Journal of Neuroscience.

[12]  T. Abel,et al.  Combinatorial chromatin modifications and memory storage: a code for memory? , 2006, Learning & memory.

[13]  J. Sweatt,et al.  The Mitogen-Activated Protein Kinase Cascade Couples PKA and PKC to cAMP Response Element Binding Protein Phosphorylation in Area CA1 of Hippocampus , 1999, The Journal of Neuroscience.

[14]  Sweatt Jd,et al.  Epigenetic mechanisms: a common theme in vertebrate and invertebrate memory formation. , 2006 .

[15]  J. Sweatt,et al.  Epigenetic Regulation of bdnf Gene Transcription in the Consolidation of Fear Memory , 2008, The Journal of Neuroscience.

[16]  J. Reul,et al.  Epigenetic mechanisms in the dentate gyrus act as a molecular switch in hippocampus-associated memory formation , 2009, Epigenetics.

[17]  D. Molfese,et al.  Histone Methylation Regulates Memory Formation , 2010, The Journal of Neuroscience.

[18]  H. Zoghbi,et al.  Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. , 2004, Human molecular genetics.

[19]  Dustin E. Schones,et al.  High-Resolution Profiling of Histone Methylations in the Human Genome , 2007, Cell.

[20]  J. David Sweatt,et al.  The MAPK cascade is required for mammalian associative learning , 1998, Nature Neuroscience.

[21]  E. Villacres,et al.  Induction of CRE-Mediated Gene Expression by Stimuli That Generate Long-Lasting LTP in Area CA1 of the Hippocampus , 1996, Neuron.

[22]  C. Allis,et al.  The language of covalent histone modifications , 2000, Nature.

[23]  Christian Rosenmund,et al.  MeCP2 Controls Excitatory Synaptic Strength by Regulating Glutamatergic Synapse Number , 2007, Neuron.

[24]  M. Montminy,et al.  Characteristics of the cAMP response unit. , 1990, Recent progress in hormone research.

[25]  Guanghua Xiao,et al.  Genome-wide Analysis of Chromatin Regulation by Cocaine Reveals a Role for Sirtuins , 2009, Neuron.

[26]  M. Szyf,et al.  Epigenetic tête-à-tête: the bilateral relationship between chromatin modifications and DNA methylation. , 2006, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[27]  T. Murphy,et al.  Differential regulation of calcium/calmodulin-dependent protein kinase II and p42 MAP kinase activity by synaptic transmission , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  J. Sweatt,et al.  Cortical DNA methylation maintains remote memory , 2010, Nature Neuroscience.

[29]  I. Izquierdo,et al.  Persistence of Long-Term Memory Storage Requires a Late Protein Synthesis- and BDNF- Dependent Phase in the Hippocampus , 2007, Neuron.

[30]  Li-Huei Tsai,et al.  Recovery of learning and memory is associated with chromatin remodelling , 2007, Nature.

[31]  Kevin Struhl,et al.  Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. , 2003, Molecular cell.

[32]  E. Kandel,et al.  Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. , 1993, Science.

[33]  Arturas Petronis,et al.  Epigenetics as a unifying principle in the aetiology of complex traits and diseases , 2010, Nature.

[34]  Emmanuel Roze,et al.  Role of the ERK/MSK1 signalling pathway in chromatin remodelling and brain responses to drugs of abuse , 2009, Journal of neurochemistry.

[35]  S. Hyman,et al.  Addiction, Dopamine, and the Molecular Mechanisms of Memory , 2000, Neuron.

[36]  Dongmei Wang,et al.  Effect of 5-aza-2-deoxycytidine microinjecting into hippocampus and prelimbic cortex on acquisition and retrieval of cocaine-induced place preference in C57BL/6 mice. , 2010, European journal of pharmacology.

[37]  C. Allis,et al.  Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. , 2000, Molecular cell.

[38]  M. Mayford,et al.  CBP Histone Acetyltransferase Activity Is a Critical Component of Memory Consolidation , 2004, Neuron.

[39]  B. Turner,et al.  Defining an epigenetic code , 2007, Nature Cell Biology.

[40]  Y. Shaham,et al.  Time-Dependent Increases in Brain-Derived Neurotrophic Factor Protein Levels within the Mesolimbic Dopamine System after Withdrawal from Cocaine: Implications for Incubation of Cocaine Craving , 2003, The Journal of Neuroscience.

[41]  H. Zoghbi,et al.  Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. , 2005, Human molecular genetics.

[42]  A. Bird,et al.  The methyl-CpG binding protein MeCP2 is essential for embryonic development in the mouse , 1996, Nature Genetics.

[43]  Scott T. Wong,et al.  Cross Talk between ERK and PKA Is Required for Ca2+ Stimulation of CREB-Dependent Transcription and ERK Nuclear Translocation , 1998, Neuron.

[44]  E. Nedivi,et al.  The function of activity-regulated genes in the nervous system. , 2009, Physiological reviews.

[45]  K. McManus,et al.  CBP, a transcriptional coactivator and acetyltransferase. , 2001, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[46]  B. Howard,et al.  The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases , 1996, Cell.

[47]  Lennart Opitz,et al.  Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice , 2010, Science.

[48]  R. Ng,et al.  Epigenetic inheritance of cell differentiation status , 2008, Cell cycle.

[49]  Scott J. Russo,et al.  Chromatin Remodeling Is a Key Mechanism Underlying Cocaine-Induced Plasticity in Striatum , 2005, Neuron.

[50]  J. David Sweatt,et al.  Activation of p42 Mitogen-activated Protein Kinase in Hippocampal Long Term Potentiation* , 1996, The Journal of Biological Chemistry.

[51]  Paul Greengard,et al.  Essential Role of the Histone Methyltransferase G9a in Cocaine-Induced Plasticity , 2010, Science.

[52]  T. Nilsen,et al.  Expansion of the eukaryotic proteome by alternative splicing , 2010, Nature.

[53]  M. Bollen,et al.  Protein Phosphatase 1 Regulates the Histone Code for Long-Term Memory , 2009, The Journal of Neuroscience.

[54]  U. Frey,et al.  Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro , 1988, Brain Research.

[55]  Michael J Meaney,et al.  Epigenetic programming by maternal behavior , 2004, Nature Neuroscience.

[56]  J. Sweatt,et al.  Reelin and ApoE Receptors Cooperate to Enhance Hippocampal Synaptic Plasticity and Learning* , 2002, The Journal of Biological Chemistry.

[57]  L. Squire,et al.  Protein synthesis and memory: a review. , 1984, Psychological bulletin.

[58]  P. Kenny,et al.  MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212 , 2010, Nature Neuroscience.

[59]  J. Herz,et al.  Reelin, lipoprotein receptors and synaptic plasticity , 2006, Nature Reviews Neuroscience.

[60]  J. Sweatt,et al.  DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity , 2008, Neurobiology of Learning and Memory.

[61]  M. Szyf,et al.  Demethylase Activity Is Directed by Histone Acetylation* , 2001, The Journal of Biological Chemistry.

[62]  D. Molfese,et al.  Regulation of Histone Acetylation during Memory Formation in the Hippocampus* , 2004, Journal of Biological Chemistry.

[63]  D. Baird.  Regulation of cAMP-inducible genes by CREB , 1990 .

[64]  J. Sweatt,et al.  Lasting Epigenetic Influence of Early-Life Adversity on the BDNF Gene , 2009, Biological Psychiatry.

[65]  Michael P. Stryker,et al.  Reversing Neurodevelopmental Disorders in Adults , 2008, Neuron.

[66]  Gregor Eichele,et al.  Mutation of the Angelman Ubiquitin Ligase in Mice Causes Increased Cytoplasmic p53 and Deficits of Contextual Learning and Long-Term Potentiation , 1998, Neuron.

[67]  D. Storm,et al.  Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 during Fear Conditioning , 2007, Neuron.

[68]  Michael Davis,et al.  Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Involvement in Amygdala-Dependent Fear Conditioning , 2004, The Journal of Neuroscience.

[69]  B. Aragona,et al.  A Critical Role for Nucleus Accumbens Dopamine in Partner-Preference Formation in Male Prairie Voles , 2003, The Journal of Neuroscience.

[70]  Edwin Smith,et al.  The Language of Histone Crosstalk , 2010, Cell.

[71]  Ted Abel,et al.  Recombinant BDNF Rescues Deficits in Basal Synaptic Transmission and Hippocampal LTP in BDNF Knockout Mice , 1996, Neuron.

[72]  Juan I. Young,et al.  Mice with Truncated MeCP2 Recapitulate Many Rett Syndrome Features and Display Hyperacetylation of Histone H3 , 2002, Neuron.

[73]  K. Berridge,et al.  The Neuroscience of Natural Rewards: Relevance to Addictive Drugs , 2002, The Journal of Neuroscience.

[74]  T. Carew,et al.  The roles of MAPK cascades in synaptic plasticity and memory in Aplysia: facilitatory effects and inhibitory constraints. , 2004, Learning & memory.

[75]  Guanghua Xiao,et al.  Histone Deacetylase 5 Epigenetically Controls Behavioral Adaptations to Chronic Emotional Stimuli , 2007, Neuron.

[76]  Paolo Sassone-Corsi,et al.  Decoding the Epigenetic Language of Neuronal Plasticity , 2008, Neuron.

[77]  Eric C. Griffith,et al.  Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation , 2006, Neuron.

[78]  Guoping Fan,et al.  Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons , 2010, Nature Neuroscience.

[79]  H. Zoghbi,et al.  Learning and Memory and Synaptic Plasticity Are Impaired in a Mouse Model of Rett Syndrome , 2006, The Journal of Neuroscience.

[80]  Danny Reinberg,et al.  Histones: annotating chromatin. , 2009, Annual review of genetics.

[81]  W. Biggs,et al.  A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence , 1989, Nature.

[82]  Axel Imhof,et al.  Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9 , 2005, Nature chemical biology.

[83]  J. Sweatt,et al.  ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning. , 2006, Learning & memory.

[84]  Stephen T. C. Wong,et al.  MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription , 2008, Science.

[85]  E. Kandel,et al.  Chromatin Acetylation, Memory, and LTP Are Impaired in CBP+/− Mice A Model for the Cognitive Deficit in Rubinstein-Taybi Syndrome and Its Amelioration , 2004, Neuron.

[86]  L. Mahadevan,et al.  Acetyllysine-binding and function of bromodomain-containing proteins in chromatin. , 2001, Frontiers in bioscience : a journal and virtual library.

[87]  J. David Sweatt,et al.  A Requirement for the Mitogen-activated Protein Kinase Cascade in Hippocampal Long Term Potentiation* , 1997, The Journal of Biological Chemistry.

[88]  Dimitris Thanos,et al.  Integration of Long-Term-Memory-Related Synaptic Plasticity Involves Bidirectional Regulation of Gene Expression and Chromatin Structure , 2002, Cell.

[89]  David R. Liu,et al.  Conversion of 5-Methylcytosine to 5- Hydroxymethylcytosine in Mammalian DNA by the MLL Partner TET1 , 2009 .

[90]  R. Huganir,et al.  MAPK cascade signalling and synaptic plasticity , 2004, Nature Reviews Neuroscience.

[91]  Catherine Dulac.  Brain function and chromatin plasticity , 2010, Nature.

[92]  R. Jaenisch,et al.  Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function , 2009, Proceedings of the National Academy of Sciences.

[93]  J. Sweatt,et al.  Covalent Modification of DNA Regulates Memory Formation , 2007, Neuron.

[94]  Courtney A Miller,et al.  Inhibitors of Class 1 Histone Deacetylases Reverse Contextual Memory Deficits in a Mouse Model of Alzheimer's Disease , 2010, Neuropsychopharmacology.

[95]  Michael Q. Zhang,et al.  Combinatorial patterns of histone acetylations and methylations in the human genome , 2008, Nature Genetics.

[96]  Denis Hervé,et al.  ERK2: a logical AND gate critical for drug-induced plasticity? , 2007, Current opinion in pharmacology.

[97]  Karl Mechtler,et al.  Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. , 2007, Molecular cell.

[98]  J. Day.  Extracellular Signal-Related Kinase Activation During Natural Reward Learning: A Physiological Role for Phasic Nucleus Accumbens Dopamine? , 2008, The Journal of Neuroscience.

[99]  R. Rodriguiz,et al.  MeCP2 in the Nucleus Accumbens Contributes to Neural and Behavioral Responses to Psychostimulants , 2010, Nature Neuroscience.

[100]  T. Insel,et al.  Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds , 2006, Nature Neuroscience.

[101]  Alcino J. Silva,et al.  CREB and memory. , 1998, Annual review of neuroscience.

[102]  L. Thompson,et al.  Therapeutic application of histone deacetylase inhibitors for central nervous system disorders , 2008, Nature Reviews Drug Discovery.

[103]  Yang Shi,et al.  Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1 , 2004, Cell.

[104]  M. Shiflett,et al.  Appetitive Pavlovian conditioned stimuli increase CREB phosphorylation in the nucleus accumbens , 2009, Neurobiology of Learning and Memory.

[105]  E. Nestler,et al.  Molecular basis of long-term plasticity underlying addiction , 2001, Nature Reviews Neuroscience.

[106]  H. Zoghbi,et al.  Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. , 1999, American journal of human genetics.

[107]  M. Szyf.  Epigenetics, DNA methylation, and chromatin modifying drugs. , 2009, Annual review of pharmacology and toxicology.

[108]  P. Greengard,et al.  Control of Cognition and Adaptive Behavior by the GLP/G9a Epigenetic Suppressor Complex , 2009, Neuron.

[109]  N. Heintz,et al.  The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain , 2009, Science.

[110]  Marcelo A Wood,et al.  A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and the expression of specific target genes. , 2006, Learning & memory.

[111]  A. Kelley.  Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning , 2004, Neuroscience & Biobehavioral Reviews.

[112]  T. Kouzarides,et al.  The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. , 2003, Nucleic acids research.

[113]  K. Brami-Cherrier,et al.  Glutamate induces histone H3 phosphorylation but not acetylation in striatal neurons: role of mitogen‐ and stress‐activated kinase‐1 , 2006, Journal of neurochemistry.

[114]  J. Morrison,et al.  Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens , 2010, Nature Neuroscience.

[115]  E. Valjent,et al.  Mitogen-activated protein kinase/extracellular signal-regulated kinase induced gene regulation in brain: a molecular substrate for learning and memory? , 2001, Molecular neurobiology.

[116]  B Kolb,et al.  Persistent Structural Modifications in Nucleus Accumbens and Prefrontal Cortex Neurons Produced by Previous Experience with Amphetamine , 1997, The Journal of Neuroscience.

[117]  A. Bird,et al.  Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). , 2004, Nucleic acids research.

[118]  James H. Eubanks,et al.  Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome , 2006, Neurobiology of Disease.

[119]  Yang Shi,et al.  Dynamic regulation of histone lysine methylation by demethylases. , 2007, Molecular cell.

[120]  Armin Schumacher,et al.  The Nuclear Kinase Mitogen- and Stress-Activated Protein Kinase 1 Regulates Hippocampal Chromatin Remodeling in Memory Formation , 2007, The Journal of Neuroscience.

[121]  S. Hyman,et al.  Neural mechanisms of addiction: the role of reward-related learning and memory. , 2006, Annual review of neuroscience.

[122]  C. Alberini.  The role of protein synthesis during the labile phases of memory: Revisiting the skepticism , 2008, Neurobiology of Learning and Memory.

[123]  K. Deisseroth,et al.  Signaling from Synapse to Nucleus: Postsynaptic CREB Phosphorylation during Multiple Forms of Hippocampal Synaptic Plasticity , 1996, Neuron.

[124]  J. Girault,et al.  Parsing Molecular and Behavioral Effects of Cocaine in Mitogen- and Stress-Activated Protein Kinase-1-Deficient Mice , 2005, The Journal of Neuroscience.

[125]  Michael B. Stadler,et al.  Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome , 2007, Nature Genetics.

[126]  C. McClung,et al.  Regulation of gene expression and cocaine reward by CREB and DeltaFosB. , 2003, Nature neuroscience.

[127]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[128]  A. Bird,et al.  DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG. , 2005, Molecular cell.

[129]  J. Sweatt,et al.  Cognitive neuroepigenetics: A role for epigenetic mechanisms in learning and memory , 2011, Neurobiology of Learning and Memory.

[130]  N. Nag,et al.  Behavioral and anatomical abnormalities in Mecp2 mutant mice: A model for Rett syndrome , 2007, Neuroscience.

[131]  Michael E. Greenberg,et al.  CREB: A mediator of long-term memory from mollusks to mammals , 1994, Cell.

[132]  M. Shiflett,et al.  Cue-Elicited Reward-Seeking Requires Extracellular Signal-Regulated Kinase Activation in the Nucleus Accumbens , 2008, The Journal of Neuroscience.

[133]  P. Tam,et al.  Mecp2 deficiency is associated with learning and cognitive deficits and altered gene activity in the hippocampal region of mice. , 2006, Brain : a journal of neurology.

[134]  James P. Curley,et al.  Epigenetic mechanisms mediating the long-term effects of maternal care on development , 2009, Neuroscience & Biobehavioral Reviews.

[135]  J. Sweatt,et al.  Epigenetic mechanisms: a common theme in vertebrate and invertebrate memory formation. , 2006, Cellular and molecular life sciences : CMLS.

[136]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[137]  T. Bredy,et al.  Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. , 2007, Learning & memory.

[138]  J. Sweatt,et al.  DNA methylation and memory formation , 2010, Nature Neuroscience.

[139]  K. Lattal,et al.  Modulation of Chromatin Modification Facilitates Extinction of Cocaine-Induced Conditioned Place Preference , 2010, Biological Psychiatry.

[140]  K. Malinovskaja,et al.  DNA Methylation Regulates Cocaine-Induced Behavioral Sensitization in Mice , 2010, Neuropsychopharmacology.

[141]  Yi Zhang,et al.  New Nomenclature for Chromatin-Modifying Enzymes , 2007, Cell.

[142]  Eric C. Griffith,et al.  Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2 , 2003, Science.

[143]  A. Shaywitz,et al.  CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. , 1999, Annual review of biochemistry.

[144]  T. Carew,et al.  Memory , 2006, Cellular and Molecular Life Sciences CMLS.

[145]  Michel Cyr,et al.  Intrastriatal inhibition of extracellular signal-regulated kinases impaired the consolidation phase of motor skill learning , 2010, Neurobiology of Learning and Memory.

[146]  M E Greenberg,et al.  Stimulation of protein tyrosine phosphorylation by NMDA receptor activation , 1991, Science.

[147]  J. David Sweatt,et al.  Evidence That DNA (Cytosine-5) Methyltransferase Regulates Synaptic Plasticity in the Hippocampus* , 2006, Journal of Biological Chemistry.

[148]  David Haig,et al.  Sex-Specific Parent-of-Origin Allelic Expression in the Mouse Brain , 2010, Science.

[149]  A. Imhof,et al.  Every methyl counts – Epigenetic calculus , 2011, FEBS letters.

[150]  I. Weaver,et al.  Acetylation-Induced Transcription Is Required for Active DNA Demethylation in Methylation-Silenced Genes , 2007, Molecular and Cellular Biology.

[151]  A. Bird,et al.  A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome , 2001, Nature Genetics.

[152]  David Belin,et al.  Evidence for Addiction-like Behavior in the Rat , 2004, Science.

[153]  S. Smith‐Roe,et al.  Response-reinforcement learning is dependent on N-methyl-D-aspartate receptor activation in the nucleus accumbens core. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[154]  E. Valjent,et al.  Mitogen-activated protein kinase/extracellular signal-regulated kinase induced gene regulation in brain , 2001, Molecular Neurobiology.

[155]  J. Sweatt,et al.  Increased Histone Acetyltransferase and Lysine Acetyltransferase Activity and Biphasic Activation of the ERK/RSK Cascade in Insular Cortex During Novel Taste Learning , 2001, The Journal of Neuroscience.

[156]  J. Girault,et al.  Opposing Patterns of Signaling Activation in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol , 2008, The Journal of Neuroscience.

[157]  Steven W. Flavell,et al.  Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system. , 2008, Annual review of neuroscience.

[158]  B. Blencowe,et al.  Regulation of Alternative Splicing by Histone Modifications , 2010, Science.

[159]  S. Haggarty,et al.  HDAC2 negatively regulates memory formation and synaptic plasticity , 2009, Nature.

[160]  J. Sweatt,et al.  The IκB Kinase Regulates Chromatin Structure during Reconsolidation of Conditioned Fear Memories , 2007, Neuron.

[161]  E. Nestler,et al.  Epigenetic mechanisms in drug addiction. , 2008, Trends in molecular medicine.

[162]  T. Murphy,et al.  Activation of p42 Mitogen‐Activated Protein Kinase by Glutamate Receptor Stimulation in Rat Primary Cortical Cultures , 1993, Journal of neurochemistry.

[163]  Tony Kouzarides,et al.  The Methyl-CpG-binding Protein MeCP2 Links DNA Methylation to Histone Methylation* , 2003, The Journal of Biological Chemistry.

[164]  Sung Han,et al.  Circadian oscillation of hippocampal MAPK activity and cAMP: implications for memory persistence , 2008, Nature Neuroscience.

[165]  S. Hyman.  Addiction: A Disease of Learning and Memory , 2007 .

[166]  Yoichi Shinkai,et al.  SET Domain-containing Protein, G9a, Is a Novel Lysine-preferring Mammalian Histone Methyltransferase with Hyperactivity and Specific Selectivity to Lysines 9 and 27 of Histone H3* , 2001, The Journal of Biological Chemistry.

[167]  L. W. Yuan,et al.  Histone acetylation by p300 is involved in CREB-mediated transcription on chromatin. , 2001, Biochimica et biophysica acta.

[168]  Benjamin A. Garcia,et al.  Regulation of HP1–chromatin binding by histone H3 methylation and phosphorylation , 2005, Nature.

[169]  A. Barco,et al.  Selective Boosting of Transcriptional and Behavioral Responses to Drugs of Abuse by Histone Deacetylase Inhibition , 2009, Neuropsychopharmacology.

[170]  Eric C. Griffith,et al.  CREB Transcriptional Activity in Neurons Is Regulated by Multiple, Calcium-Specific Phosphorylation Events , 2002, Neuron.

[171]  J. Sweatt,et al.  Molecular Neurobiology of Human Cognition , 2002, Neuron.

[172]  Salvatore Oliviero,et al.  Histone Crosstalk between H3S10ph and H4K16ac Generates a Histone Code that Mediates Transcription Elongation , 2009, Cell.

[173]  B M Turner,et al.  Histone acetylation and an epigenetic code. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[174]  Joel M Stein,et al.  Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional Activation , 2007, The Journal of Neuroscience.

[175]  H. Zoghbi,et al.  Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 , 1999, Nature Genetics.

[176]  A. Bird.  DNA methylation patterns and epigenetic memory. , 2002, Genes & development.