Epigenetics

1. Auflage 2014
ISBN: 978-0-12-801472-1
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band 115, 344 Seiten

Reihe: International Review of Neurobiology

This well-established international series examines major areas of basic and clinical research within neuroscience, as well as emerging and promising subfields. This volume concentrates on Epigenetics - This book looks at Epigeneticsin the light of the newest scholarly discoveries and insights

Autoren/Hrsg.

Inhaltsverzeichnis

1;Front Cover;1
2;Epigenetics;4
3;Copyright;5
4;Contents;6
5;Contributors;10
6;Preface;12
7;Chapter One: Environmental Alterations of Epigenetics Prior to the Birth;16
7.1;1. Introduction;17
7.2;2. Manifestation of Environmental Factors;19
7.2.1;2.1. Substances of abuse;19
7.2.1.1;2.1.1. Drinking;19
7.2.1.2;2.1.2. Smoking;25
7.2.1.3;2.1.3. Cocaine;25
7.2.1.4;2.1.4. Cannabis;26
7.2.1.5;2.1.5. Opioid;27
7.2.1.6;2.1.6. Methamphetamine;27
7.2.2;2.2. Diet and nutrition;28
7.2.2.1;2.2.1. Folic acid;28
7.2.2.2;2.2.2. Caffeine;29
7.2.3;2.3. Prescriptive medicine;29
7.2.3.1;2.3.1. Valproic acid;29
7.2.3.2;2.3.2. .-Hydroxybutyrate;30
7.2.4;2.4. Environmental toxins and pollutants;30
7.2.4.1;2.4.1. Arsenic;30
7.2.4.2;2.4.2. Lead;31
7.2.4.3;2.4.3. Cadmium;31
7.2.4.4;2.4.4. Methyl mercury;31
7.2.4.5;2.4.5. Bisphenol A;32
7.2.5;2.5. Stress and aversive life experience;33
7.3;3. Mechanisms of Environmentally Induced Epigenetic Changes;34
7.3.1;3.1. On DNA methylation;34
7.3.2;3.2. On histone modification;38
7.3.3;3.3. On miRNA and other noncoding RNA;38
7.3.4;3.4. On transposable elements;39
7.4;4. Effect of Epigenetic Alterations on Neurodevelopment;40
7.4.1;4.1. Epigenetic functional concerns;40
7.4.2;4.2. Intrinsic epigenetic program;41
7.4.3;4.3. Alcohol drinking, epigenetics phenotypes, and FASDs;45
7.4.3.1;4.3.1. Effect on germline and placenta;46
7.4.3.2;4.3.2. Effect on embryonic and early brain development;46
7.4.3.3;4.3.3. Potential late-onset effect;47
7.4.3.4;4.3.4. Transgenerational effect;48
7.5;Acknowledgments;49
7.6;References;49
8;Chapter Two: Transgenerational Epigenetics and Brain Disorders;66
8.1;1. Introduction to Transgenerational Epigenetic Inheritance;66
8.2;2. Epigenetics and Epigenetic Processes;68
8.3;3. Evidence for Transgenerational Epigenetic Inheritance;70
8.4;4. Germline-Independent Epigenetic Inheritance;72
8.5;5. Germline-Dependent Epigenetic Transmission;72
8.6;6. Transgenerational Epigenetic Effects on Brain Disorders;75
8.7;7. Concluding Remarks;81
8.8;Acknowledgment;81
8.9;References;82
9;Chapter Three: The Epigenetic Landscape of Alcoholism;90
9.1;1. Introduction;91
9.2;2. Epigenetic Regulation due to Histone Covalent Modifications;93
9.2.1;2.1. Role of histone acetylation and deacetylation in transcriptional regulation;93
9.2.2;2.2. Alcohol and histone acetylation and deacetylation mechanisms in the brain;96
9.2.3;2.3. Role of HDACs in alcoholism;97
9.2.4;2.4. Alcohol and histone acetylation and deacetylation mechanisms in nonneuronal tissues;100
9.2.5;2.5. Other drugs of abuse and histone acetylation and deacetylation mechanisms;101
9.2.6;2.6. Alcohol and histone methylation mechanisms;102
9.2.7;2.7. Alcohol and histone phosphorylation mechanisms;103
9.3;3. Epigenetic Regulation due to DNA Methylation;104
9.3.1;3.1. Functions of DNMTs and MBDs;105
9.3.2;3.2. DNA demethylation pathways in the brain;106
9.3.3;3.3. Alcohol and DNA methylation and demethylation mechanisms;106
9.3.4;3.4. Alcohol and DNA methylation mechanisms in nonneuronal tissues;108
9.3.5;3.5. Other drugs of abuse and DNA methylation mechanisms;108
9.3.6;3.6. DNMT inhibitors as a therapy for drug addiction;109
9.3.7;3.7. Epigenetics of adolescent drinking and implications for alcohol phenotypes in later life;111
9.3.8;3.8. Epigenetic regulation of glial-neuronal interactions and alcohol;112
9.4;4. Genome-Wide Approaches to Understand the Basis of Alcoholism;113
9.5;5. Using Invertebrate Models to Study the Basis of Ethanol Phenotypes;114
9.6;6. Inheritance of a Drug Phenotype;115
9.7;7. Conclusions;116
9.8;Acknowledgments;118
9.9;References;119
10;Chapter Four: Epigenetic Regulatory Mechanisms in Stress-Induced Behavior;132
10.1;1. Introduction;133
10.2;2. Stress-Induced Neural and Behavioral changes in Adulthood and the Epigenetic Mechanisms Involved;134
10.2.1;2.1. Histone lysine acetylation and deacetylation in stress-induced neural and behavioral responses;135
10.2.1.1;2.1.1. Histone acetyl transferases;135
10.2.1.2;2.1.2. Histone deacetylases;136
10.2.2;2.2. Histone lysine acetylation and deacetylation in stress responses;136
10.2.2.1;2.2.1. HDACi as potential therapeutics for psychiatric and neurodegenerative disorders;142
10.2.3;2.3. Histone lysine methylation and demethylation in stress-induced neural and behavioral responses;143
10.2.3.1;2.3.1. Histone lysine methyltransferases and demethylases;143
10.2.3.2;2.3.2. Histone methylation in neuropsychiatric disorders;144
10.2.3.3;2.3.3. Histone lysine methylation in stress-mediated effects on the hippocampal neurogenesis;150
10.2.3.4;2.3.4. KMTs and KDMs as potential drug targets;151
10.3;3. DNA Methylation and Demethylation in Stress-Induced Neural and Behavioral Responses;153
10.4;4. Role of Noncoding RNAs in Epigenetic Regulation of Stress-Mediated Effects;154
10.5;5. Early-Life Stress-Induced Adult Onset Behavioral Disorders and the Epigenetic Mechanisms Involved;159
10.5.1;5.1. Histone lysine acetylation/deacetylation, methylation/demethylation, and DNA methylation in stress-induced neural an...;159
10.6;6. Conclusion;161
10.7;Acknowledgments;162
10.8;References;162
11;Chapter Five: Epigenetics of Schizophrenia: An Open and Shut Case;170
11.1;1. Introduction;171
11.2;2. An Epigenetics Primer;172
11.3;3. Heterochromatization;172
11.3.1;3.1. DNA methylation;172
11.3.2;3.2. Restrictive histone modifications;175
11.3.3;3.3. The heterochromatization positive feedback loop;176
11.4;4. Euchromatization;176
11.4.1;4.1. Relaxing histone modifications;177
11.4.2;4.2. DNA demethylation;177
11.5;5. Schizophrenia and Epigenetics;182
11.5.1;5.1. Restrictive chromatin and schizophrenia;182
11.5.2;5.2. Permissive chromatin and schizophrenia;189
11.5.3;5.3. Dysregulated chromatin and schizophrenia;191
11.6;6. Fulfilling the Promise of Epigenetics in Schizophrenia;193
11.6.1;6.1. Therapeutics: Targeting the epigenome;193
11.6.2;6.2. How do current antipsychotics affect the epigenome?;193
11.6.3;6.3. Relaxing the epigenome;194
11.6.4;6.4. Silencing the epigenome;196
11.6.5;6.5. Blood cells to monitor disease course and individualize treatment;197
11.7;7. Conclusion;199
11.8;Acknowledgments;199
11.9;References;199
11.10;Further Reading;216
12;Chapter Six: Epigenetic Mechanisms in Autism Spectrum Disorder;218
12.1;1. Introduction;219
12.2;2. Molecular Aspects of Epigenetic Mechanisms;221
12.2.1;2.1. Histones;221
12.2.2;2.2. DNA methylation;224
12.2.3;2.3. DNA hydroxymethylation;227
12.3;3. Genetic Defects with Epigenetic Implications;228
12.3.1;3.1. Methyl-CpG-binding protein 2 (MECP2);229
12.3.2;3.2. DNA topoisomerase;231
12.3.3;3.3. Chromodomain helicase DNA-binding protein 8;232
12.4;4. Epigenetic Dysregulation of ASD Candidate Genes;233
12.4.1;4.1. GABAergic genes;233
12.4.2;4.2. GAD67 (GAD1);234
12.4.3;4.3. Reelin;235
12.4.4;4.4. GABA ß3;237
12.4.5;4.5. Oxytocin receptor (OXTR);238
12.4.6;4.6. Brain-derived neutrophic factor (BDNF);238
12.4.7;4.7. Ubiquitin-protein ligase E3A (UBE3A);239
12.4.8;4.8. Engrailed-2 (EN-2);240
12.4.9;4.9. SH3 and multiple ankyrin repeat domains (SHANK3);241
12.5;5. Environmental Model of Autism;242
12.6;6. Conclusions;244
12.7;Acknowledgments;246
12.8;References;246
13;Chapter Seven: MicroRNAs and Ethanol Toxicity;260
13.1;1. Introduction;261
13.2;2. miRNAs and Their Biogenesis;262
13.2.1;2.1. Biogenesis of miRNAs;264
13.3;3. Mechanisms of miRNA Function;267
13.3.1;3.1. Targeting 3'UTRs for mRNA degradation and translation repression;267
13.3.2;3.2. Alternate functions of miRNAs;268
13.3.2.1;3.2.1. Transcription control and regulation of heterochromatin;269
13.3.2.2;3.2.2. Secreted miRNAs: Potential endocrine and signaling molecules?;271
13.4;4. miRNAs as Mediators of Ethanol Effects in Developing and Adult Tissues;273
13.4.1;4.1. miR-9: An example of a common developmental and adult ethanol target;277
13.4.1.1;4.1.1. Developmental effects of ethanol on miR-9;280
13.4.1.2;4.1.2. miR-9 as an adult target of ethanol;281
13.4.2;4.2. Ethanol and epigenetic control over miRNA expression;282
13.4.2.1;4.2.1. The miR-9 genes are an example of an epigenetically regulated miRNA family;283
13.4.2.2;4.2.2. Evidence for epigenetic regulation of miR-9 in tumor biology;284
13.4.2.3;4.2.3. A role for ethanol in epigenetic regulation of miR-9;284
13.4.3;4.3. Ethanol-sensitive miRNAs as mediators of epigenetic control;285
13.5;5. miRNA-Mediated Transgenerational Inheritance of Information: A Novel Mechanism for Transgenerational Transfer of Epimut ...;286
13.6;6. Conclusions;288
13.7;Acknowledgments;290
13.8;References;290
14;Index;300
15;Contents of Recent Volumes;306

Leseproben

Chapter Two Transgenerational Epigenetics and Brain Disorders
Nadia Rachdaoui; Dipak K. Sarkar1    Rutgers Endocrine Research Program, Department of Animal Sciences, Rutgers University, New Brunswick, New Jersey, USA
1 Corresponding author: email address: [e-mail] Abstract
Neurobehavioral and psychiatric disorders are complex diseases with a strong heritable component; however, to date, genome-wide association studies failed to identify the genetic loci involved in the etiology of these brain disorders. Recently, transgenerational epigenetic inheritance has emerged as an important factor playing a pivotal role in the inheritance of brain disorders. This field of research provides evidence that environmentally induced epigenetic changes in the germline during embryonic development can be transmitted for multiple generations and may contribute to the etiology of brain disease heritability. In this review, we discuss some of the most recent findings on transgenerational epigenetic inheritance. We particularly discuss the findings on the epigenetic mechanisms involved in the heritability of alcohol-induced neurobehavioral disorders such as fetal alcohol spectrum disorders. Keywords Neuronal disease DNA methylation Histone Inheritance Germline Transgenerational 1 Introduction to Transgenerational Epigenetic Inheritance
Most complex human diseases such as cancer and psychiatric disorders are governed by a genetic heritable component; however, to date, genome-wide association studies failed to identify the causal loci and genetic basis of most complex diseases (Gibson, 2011). This “missing heritability” suggests that, in addition to genetically inherited information through particular loci, additional layers of information referred to as epigenetics play an important role in the inheritance of complex diseases (Bohacek & Mansuy, 2013; Danchin et al., 2011). Acquired epigenetic marks are thought to be completely erased between generations; however, several studies have shown that this epigenetic information can be transmitted through the germline. This phenomenon is known as “transgenerational epigenetic inheritance” (Daxinger & Whitelaw, 2010; Horsthemke, 2007). Moreover, the discovery of parental imprinting also called “genomic imprinting” in the 1980s provided the first evidence that epigenetic processes persist between generations and might underlie the transgenerational epigenetic inheritance of traits and diseases (Kearns, Preis, McDonald, Morris, & Whitelaw, 2000; Reik, Collick, Norris, Barton, & Surani, 1987; Swain, Stewart, & Leder, 1987; Tost, 2009). Genomic imprinting is a non-Mendelian form of gene regulation that contributes to the establishment of epigenetic marks in the parental gametes (Reik & Walter, 2001). The mechanisms for gene imprinting are still not fully elucidated; however, it is believed that they involve epigenetic silencing through methylation of CpG-rich domains in a parent-specific manner during gametonenesis (Pfeifer, 2000). This phenomenon results in the preferential expression of specific genes from the allele inherited either from the father or from the mother. For example, the imprinted gene insulin-like growth factor 2 (Igf2), which was shown to play an important role in fetal development and growth, is exclusively expressed from the paternal allele; the maternally inherited allele for Igf2 is epigenetically silenced (Chao & D'Amore, 2008). Because of these epigenetically mediated allele-specific gene expressions, imprinted genes are believed to be especially susceptible to epigenetic dysregulation by environmental factors, such as nutrition, stress, and toxic agents. For example, it was shown that maternal exposure to methyl-deficient diets during pregnancy can alter the expression of imprinted genes (Bekdash, Zhang, & Sarkar, 2013; Waterland, Lin, Smith, & Jirtle, 2006). When these imprinting aberrations occur during early fetal development, they are often manifested as developmental and neurological disorders. Evidence shows that among the different organs, the brain is the most enriched tissue in imprinted genes (Prickett & Oakey, 2012) and, therefore, the most vulnerable to environmental perturbations (Jirtle & Skinner, 2007). Several research studies have reported that early-life exposure to environmental factors such as stress, drugs, and toxins can alter the epigenetic status of imprinted genes and other genes important to brain development and result in neurobehavioral deficiencies and psychiatric disorders (Jirtle & Skinner, 2007; Prickett & Oakey, 2012). Furthermore, it is suggested that certain inherited brain disorders such as Beckwith–Wiedemann syndrome, Rett syndrome, fragile X syndrome, and Angelman's syndrome arise from abnormal-specific imprinted genes (Kaminsky, Wang, & Petronis, 2006; Kantor, Shemer, & Razin, 2006; Weksberg, Shuman, & Smith, 2005). In this review, we describe the most recent findings on transgenerational epigenetic inheritance, particularly in relation to brain disorders. We first discuss the mounting evidence that supports the transgenerational inheritance of environmentally induced epigenetic alterations and then we describe the epigenetic mechanisms involved in the alcohol-mediated neurobehavioral and cognitive deficiencies and their role in the transgenerational transmission of alcohol's deleterious effects on brain development and function. We conclude this review by arguing that understanding the implications of these environmentally induced transgenerational epigenetic changes will extend our knowledge on human disease susceptibility and ultimately lead to the development of new diagnostic and therapeutic strategies. 2 Epigenetics and Epigenetic Processes
Richard Goldschmidt, an integrative biologist, believed that early developmental exposure to events has as much impact as genetics on the determination of the adult phenotype (Goldschmidt, 1933). It is not until 1940 that the renowned embryologist Conrad Hal Waddington attempted to bridge both fields of genetics and embryology by being the first to coin the term “epigenetics.” Waddington described development as the path from genotype to phenotype and suggested that the mechanisms by which genes guide development or epigenetic, a process influenced by the surrounding environment, should be given the name of epigenetics. In his opinion, the epigenetic processes help to bridge the gap between environmental and genetic factors. In recent years, “epigenetics” is referred to as the study of mechanisms involved in changes in genetic information and gene expression that are independent of any change in DNA sequence (i.e., mutations). This process serves to maintain different gene expression patterns during key developmental periods and contributes to the determination of different cell phenotypes. It also constitutes a dynamic process that helps translate environmental stimuli into changes in gene expression patterns (Jang & Serra, 2014; Jirtle et al., 2007; Reul, 2014). Many epigenetic processes have been identified. We look at some of the epigenetic marks that consist of DNA methylation at the carbon-5 position of cytosine on CpG dinucleotides, histone proteins posttranslational modifications (HPTMs) at their N-terminal tails by methylation, acetylation, phosphorylation, ubiquitination, ADP-ribosylation, and sumoylation and interference of gene transcription by small noncoding RNAs (sncRNAs; Kugel & Goodrich, 2012). Epigenetic marks induce changes in chromatin structure and serve as docking sites for transcription factors (i.e., activators and repressors). They are specific to each gene and are dynamically regulated by various environmental conditions. In terms of gene activity, a condensed chromatin (heterochromatin) is generally repressed, whereas an open chromatin (euchromatin) is transcriptionally active and tends to be associated with distinct epigenetic signals. Heterochromatin is often associated with methylation of CpG dinucleotides, hypoacetylation of H3 and H4, and dimethylation/trimethylation of lysine 9 on H3 (H3K9Me2,3), whereas euchromatin is associated with hypomethylation of CpG dinucleotides, acetylation of H3 and H4, and dimethylation/trimethylation of lysine 4 on H3 (H3K4Me; Shukla et al., 2008). Another mechanism involved in modulating chromatin structure is the incorporation of nonallelic histone variants of H2A, H2B, and H3, and not H4, which replace preexisting conventional histones during development and differentiation (Bosch & Suau, 1995; Brandt et al., 1979; Margueron & Reinberg, 2010; Wunsch, Reinhardt, & Lough, 1991). This selective deposition of histone variants may become predominant in the differentiated cell (Pina & Suau, 1987a, 1987b; Wunsch et al., 1991). Several enzymes are involved in these epigenetic processes. Histone acetyltransferases acetylate lysine residues on the N-terminal tail of histone proteins, decreasing its affinity for DNA and resulting in the relaxation of chromatin making it accessible to the transcription machinery. In contrast, histone deacetylases remove the acetyl...