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Handbook of Epigenetics
The New Molecular and Medical Genetics
3rd Edition - September 8, 2022
Editor: Trygve O Tollefsbol
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 9 1 9 0 9 - 8
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 1 9 5 0 - 0
Handbook of Epigenetics: The New Molecular and Medical Genetics, Third Edition provides a comprehensive analysis of epigenetics, from basic biology to clinical application. This… Read more
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Handbook of Epigenetics: The New Molecular and Medical Genetics, Third Edition provides a comprehensive analysis of epigenetics, from basic biology to clinical application. This new edition has been fully revised to cover the latest and evolving topics in epigenetics, with chapters updated and new chapters added on topics such as single-cell epigenetics, DNA methylation clocks in age-related diseases, transposable elements and epigenetics, X chromosome inactivation, and the epigenetics of drug addiction, among other topics. Throughout this edition, greater emphasis falls on epigenomic analyses and incorporating multi-omics approaches rather than gene-specific analyses.
In addition, this edition has also been enhanced with step-by-step instructions in research methods, as well as easy-to-digest disease case studies and clinical trials that provide context and applied examples of recent advances in disease understanding and epigenetic therapeutics. These features empower researchers to reproduce the approaches and studies discussed and aid clinical translation. Live links across chapters tie in relevant external datasets and resources.
- Provides a timely and comprehensive collection of fully up-to-date coverage of epigenetics
- Covers basic epigenetic biology, research methods and technology, disease relationships and clinical medicine
- Written at a verbal and technical level that can be understood by scientists and students alike, with chapter summaries and conclusions included throughout
- Discusses exciting new topics in epigenetics, such as DNA methylation clocks in age-related diseases, transposable elements and epigenetics, X chromosome inactivation, and the epigenetics of drug addiction
- Includes step-by-step instructions in research protocols to aid reproducibility, as well as easy-to-digest disease case studies and clinical trials, providing context and applied examples of recent clinical translation
Researchers working in genetics, biology, molecular biology, pharmaceutical science, and clinical therapy; university researchers, pharmaceutical company and biotechnology researchers interested in drug development and therapies. Advanced undergraduate and graduate students; clinicians
- Cover image
- Title page
- Table of Contents
- Copyright
- List of contributors
- Section I: Overview
- Chapter 1. Epigenetics Overview
- Abstract
- Outline
- Introduction
- Molecular Mechanisms of Epigenetics
- Methods in Epigenetics
- Model Organisms of Epigenetics
- Factors Influencing Epigenetic Changes
- Evolutionary Epigenetics
- Epigenetic Epidemiology
- Epigenetics and Human Disease
- Epigenetic Therapy
- The Future of Epigenetics
- Conclusion
- References
- Section II: Molecular Mechanisms of Epigenetics
- Chapter 2. Mechanisms of DNA Methylation and Demethylation During Mammalian Development
- Abstract
- Outline
- Introduction
- DNA Methylation
- DNA Demethylation
- Conclusions
- Acknowledgments
- Glossary
- Abbreviations
- References
- Chapter 3. Mechanisms of Histone Modifications
- Abstract
- Outline
- Introduction
- Main Histone Modifications
- Role of Aberrant Histone Modifications in Disease
- Conclusions
- References
- Chapter 4. The Epigenetics of Noncoding RNA
- Abstract
- Outline
- Introduction
- Conclusions
- Acknowledgments
- Abbreviations
- References
- Chapter 5. Prions and prion-like phenomena in epigenetic inheritance
- Abstract
- Outline
- Structural Heredity
- Amyloid Prions of Saccharomyces cerevisiae, Podospora anserina, and Other Organisms
- Cis Elements Important for Amyloid Prion Formation
- Genetic Control of Amyloid Prion Formation and Propagation
- Amyloid Prion Variants
- Self-Driven Assembly of Hsp60 Mitochondrial Chaperonin
- Cytotaxis of Cilia and Other Complex Structures
- Mixed Heredity: “Nonamyloid Prions” That Propagate by Auto-activation
- Regulatory Inheritance
- The Lactose Operon and Its Positive Feedback Loop
- Crippled Growth, A Self-sustained and Mitotically Inheritable Signaling Pathway in the Filamentous Fungus Podospora anserina
- The White/Opaque Switch of Candida albicans, An Epigenetic Switch at the Transcription Level
- Conclusion
- References
- Chapter 6. Higher-order Chromatin Organization in Diseases, from Chromosomal Position Effect to Phenotype Variegation
- Abstract
- Outline
- Introduction
- Chromosomal Position Effect in Human Pathologies
- Telomeric Position Effect; Implication in Human Pathologies
- Conclusions
- References
- Chapter 7. Polycomb-group proteins and epigenetic control of gene activity
- Abstract
- Outline
- Introduction
- Polycomb Repressive Complexes
- Mechanism of Gene Regulation by Polycomb Group Proteins
- PcG-Mediated Control of Gene Expression in Stem Cells to Maintain Homeostasis
- PcG-mediated Control of Gene Expression in Embryonic Stem Cells
- PcG-mediated Control of Gene Expression in Cancer Cells
- Conclusion and Future Perspective
- Acknowledgment
- References
- Section III: Methods in Epigenetics
- Chapter 8. Methods for Analyzing DNA Cytosine Modifications Genome-wide
- Abstract
- Outline
- Introduction
- Methylated DNA Immunoprecipitation
- MBD Protein-based Affinity Pulldown
- Methylated-CpG Island Recovery Assay
- Targeted Bisulfite Sequencing
- Infinium and EPIC Methylation Bead Chips
- Whole Genome Bisulfite Sequencing
- Other Sodium Bisulfite-based Approaches
- Enzymatic Methyl-sequencing and Pyrimidine Borane-based Methods
- 5-Hydroxymethylcytosine Mapping Methodologies
- TET-assisted Bisulfite Sequencing
- Oxidative Bisulfite Sequencing
- APOBEC-coupled Epigenetic Sequencing
- SMRT-seq and Nanopore Sequencing
- Single Cell Whole Genome Methylation Analysis
- Future Directions and Challenges
- Acknowledgments
- References
- Chapter 9. Genome-wide Analyses of Histone Modifications in the Mammalian Genome
- Abstract
- Outline
- Introduction
- Histone Modifications in Regulatory Regions
- High-throughput Assays for Mapping Histone Modifications
- Genome-wide Mapping of Histone Modifications
- Catalog of Histone Modification Profiles
- Variation of Histone Modifications
- Conclusions and Perspectives
- ChIP-seq Data Analysis Workflow
- Acknowledgments
- References
- Chapter 10. Techniques for Analyzing Genome-wide Expression of Non-coding RNA
- Abstract
- Outline
- Introduction
- cDNA Library Construction
- Analysis of RNA-seq Data for ncRNAs
- Estimating the Transcription and Degradation Rates of Non-Coding Transcripts
- Conclusions
- Dyrec-seq Protocol
- Acknowledgments
- Glossary
- References
- Chapter 11. Computational Epigenetics: The Competitive Endogenous RNAs Network Analysis
- Abstract
- Outline
- Introduction
- Basic Principles of Competitive Endogenous RNAs
- The Competitive Endogenous RNAs Network
- Mathematical Models for Competitive Endogenous RNAs Network Analysis
- Comparison of Mathematical Models for Competitive Endogenous RNAs Network Analysis
- Computational Epigenetic Approaches for Competitive Endogenous RNAs Network Analysis
- Conclusion
- Acknowledgments
- References
- Section IV: Model Organisms of Epigenetics
- Chapter 12. Epigenetic Mechanisms in Bacteria Bridge Physiology, Growth and Host–Pathogen Interactions
- Abstract
- Outline
- Introduction
- Protein Phosphorylation in Prokaryotes
- DNA Methylation in Bacteria
- Protein Methylation
- Crosstalks Between Epigenetic Modifications
- Conclusions and Future Perspectives
- Summary
- Protocols for Molecular Modeling
- References
- Further Reading
- Chapter 13. Drosophila Epigenetics
- Abstract
- Outline
- Introduction: Drosophila as a Model Organism in Epigenetic Research
- Epigenetic Modification of Histone Proteins Regulate Chromatin Packaging and Gene Control in Drosophila
- Position-Effect Variegation
- The Role of Epigenetics During Drosophila Development: Epigenetic Memory
- Dosage Compensation
- The Epigenetic Language in Postmitotic Neurons Underlying Cognitive Function
- Conclusion
- Protocol
- Glossary
- Abbreviations
- References
- Chapter 14. Models of Mouse Epigenetic Inheritance: Classification, Mechanisms, and Experimental Strategies
- Abstract
- Outline
- Introduction
- Epigenetic Programming in Gametogenesis
- Epigenetic Re-Programming During Embryogenesis
- Metastable Epialleles
- Genomic Imprinting
- Conclusions
- Acknowledgments
- References
- Chapter 15. Plant Epigenomics
- Abstract
- Outline
- Introduction
- Basic Mechanisms of Plant Epigenome Regulation
- Epigenetic Phenomena in Plants
- Epigenetic Regulation of Transposable Elements and Interactions With Genes
- Epigenetic Regulation of Stress Responses in Plants
- Emerging Technologies for Epigenome Studies in Plants
- Future Perspectives
- References
- Section V: Factors Influencing Epigenetic Changes
- Chapter 16. Dynamic Changes in Epigenetic Modifications During Mammalian Early Embryo Development
- Abstract
- Outline
- Introduction
- DNA methylation during mammalian early embryo development
- Dynamic changes and function of histone modifications in early embryo development
- Summary
- References
- Chapter 17. Epigenetic Biomarkers
- Abstract
- Outline
- Introduction
- Epigenetic biomarkers offer distinct advantages over genetic biomarkers
- Minimally invasive tissues are suitable for detecting epigenetic biomarkers
- Field cancerization and epigenetic biomarkers
- Potential DNA methylation biomarkers in cancer and other diseases
- Potential m6A methylation biomarkers in cancer and other diseases
- Potential histone modification biomarkers in cancer and other diseases
- Potential non-coding RNA biomarkers in diseases
- Epigenetic biomarker detection methods in the clinic
- Challenges and future perspectives
- Abbreviations
- References
- Chapter 18. Transposable Elements Shaping the Epigenome
- Abstract
- Outline
- Introduction
- Classification and structure of transposable elements
- Transposable elements genomic annotation
- Epigenetic control of transposable elements
- Factors influencing transposable elements epigenetics
- Influence of transposable elements on host epigenetics
- Concluding remarks
- References
- Chapter 19. Dietary and Metabolic Compounds Affecting Covalent Histone Modifications
- Abstract
- Outline
- Introduction
- Metabolic and Dietary Control of Histone and Transcriptional Dynamics
- Regulation of Chromatin Dynamics
- Histone Demethylation
- Histone Acetylation
- Other Histone Modifications
- Concluding Perspectives
- Acknowledgments
- Abbreviations
- References
- Further reading
- Chapter 20. Epigenetics, Stem Cells, Cellular Differentiation, and Associated Neurological Disorders and Brain Cancer
- Abstract
- Outline
- Introduction to Epigenetics
- Epigenetics and the Human Brain
- Epigenetics and Glioblastoma
- Epigenetic Changes in Glioma Stem Cells
- Genes Involved in Glioblastoma
- Stem Cell Transplantations in Glioblastoma
- Neural Stem Cell Transplantation for GB
- Conclusions
- Abbreviations
- References
- Chapter 21. Epigenetic Regulation of Skeletal Muscle Regeneration
- Abstract
- Outline
- Introduction
- Epigenetic Control in the Maintenance of Quiescence
- Epigenetic Control of the Activation and Proliferation of SCs
- Epigenetic Control of SCs Differentiation
- Small Molecules as a Therapeutic Alternative in the Epigenetic Control of Regeneration
- Conclusion
- Acknowledgments
- References
- Chapter 22. Epigenetics of X-chromosome Inactivation
- Abstract
- Outline
- Introduction
- Brief Historical Perspective of XCI
- X-chromosome Evolution and the Incomplete Nature of XCI
- Imprinted and Random XCI
- XCI Regulation and Main Epigenetic Steps
- XCI Differences Between Mice and Humans
- X-autosome Dosage Compensation
- Methods for Exploring XCI Status
- Physiological and Pathogenic XCI Skewing
- X-chromosome, Sex Bias and Diseases
- XCI Plasticity: Opportunities for Epigenetic Therapeutics
- Concluding Remarks
- Acknowledgments
- Glossary
- References
- Chapter 23. Epigenetics of Memory Processes
- Abstract
- Outline
- Introduction
- Histone Posttranslational Modifications: Long-term Memory Regulation
- Histone Acetylation and HATs
- Histone Deacetylation and Histone Deacetylases
- Histone Methylation
- Histone Modifications: Gene Expression
- Manipulating Histone Modifications
- DNA Methylation and Long-term Memory
- Histone Variant Exchange
- Epitranscriptomics: RNA Epigenetics
- Summary
- Acknowledgments
- Abbreviations
- References
- Chapter 24. Transgenerational Epigenetics
- Abstract
- Outline
- Introduction
- Epigenetic Consequences of Prenatal Maternal Exposures
- Postnatal Maternal Regulation of the Epigenome
- Paternal Influence on Offspring Development
- Transgenerational Effects of Parental Influence
- Germline-mediated Transgenerational Inheritance
- Experience-dependent Epigenetic Inheritance
- Epigenetics, Plasticity, and Evolving Concepts of Inheritance
- Summary
- Acknowledgments
- References
- Chapter 25. DNA Methylation Clocks in Age-related Disease
- Abstract
- Outline
- Aging
- Epigenetic Clocks
- First Generation Epigenetic Clocks
- Second Generation Epigenetic Clocks
- Epigenetic Clocks and Age-related Disease
- Epigenetic Clocks Without an Age-related Disease Focus
- Can Epigenetic Age be Modified?
- Summary
- References
- Section VI: Evolutionary Epigenetics
- Chapter 26. Evolution of Epigenetic Mechanisms in Plants: Insights from H3K4 and H3K27 Methyltransferases
- Abstract
- Outline
- Introduction
- Histone Lysine Methylation
- Histone Lysine Methyltransferases in Plants
- Evolution of Plant Histone Lysine Methyltransferases Methylating H3K4
- Evolution of Plant Histone Lysine Methyltransferases Methylating H3K27
- Perspectives
- Acknowledgments
- References
- Chapter 27. Evolution, Functions and Dynamics of Epigenetic Mechanisms in Animals
- Abstract
- Outline
- Introduction
- Evolution of Epigenetic Mechanisms in The Animal Kingdom
- Features of Epigenetic Mechanisms and Role in Gene Regulation
- Dynamics of Epigenetic Marks During Development
- Generation of Phenotypic Variation in Populations by Epigenetic Mechanisms
- Relevance of Epigenetics for Animal Ecology
- Relevance of Epigenetics for Animal Evolution
- Conclusions and Perspectives
- Summary
- References
- Chapter 28. Adaptive evolution and epigenetics
- Abstract
- Outline
- Introduction
- Epigenetic Variation
- Modeling Evolution
- Induced Epigenetic Changes
- Spontaneous Epigenetic Variation
- Modeling Spontaneous Epigenetic Variation
- Limits of Epigenetic Contributions to Adaptation
- Conclusions and Future Directions
- Acknowledgments
- References
- Section VII: Epigenetic Epidemiology
- Chapter 29. Epigenetics of Livestock Health, Production, and Breeding
- Abstract
- Outline
- Introduction
- Development of Animal Breeding
- Epigenetic Source of Phenotypic Variation in Livestock Health and Production
- Revisiting Animal Breeding Planning and Management: The Role of Epigenetic Mechanisms
- Conclusion
- Summary
- Livestock Epigenetics Case Study
- Acknowledgments
- Glossary
- References
- Chapter 30. Nutritional Epigenetics and Fetal Metabolic Programming
- Abstract
- Outline
- Introduction
- Metabolic Sensing by Epigenetic Mechanisms
- Impact of Prenatal Nutrition on Fetal Reprogramming
- Maternal Diet and Metabolic Epigenome
- Summary and Perspectives
- Acknowledgments
- Glossary
- References
- Chapter 31. Epigenetics of Drug Addiction
- Abstract
- Outline
- Introduction
- What Is Addiction?
- Dopamine and Reward Circuits
- Synaptic Plasticity, Learning and Memory and Addiction
- Epigenetic Processes in Drug Addiction
- Utilizing Epigenetic Targets for Diagnosis and Treatments to Combat Addiction and SUDs
- Conclusion
- Summary
- Acknowledgments
- References
- Further Reading
- Chapter 32. Environmental Influence on Epigenetics
- Abstract
- Outline
- Introduction
- The Extent (Timeline) of Environmental Influence
- Exerting Environment
- Mental or Physiological Environment
- Hazardous Environmental Pollutants and Chemicals
- Conclusion and Future Direction
- Research case study
- Acknowledgments
- Glossary
- References
- Chapter 33. Gut Microbiome Influence on Human Epigenetics, Health, and Disease
- Abstract
- Outline
- Introduction
- Early Microbiome Exposure and Epigenetic Influence
- Human Gut Microflora
- Microbiome, Epigenetics, and Effect on Metabolism
- Gut microbiota, Inflammation, and Colorectal Carcinogenesis
- Pathogenic Infections and Cancer
- Pathogenic Infections and Epigenetic Modifications
- Summary
- Abbreviations
- References
- Chapter 34. Population Pharmacoepigenomics
- Abstract
- Outline
- Introduction
- General Aspects of Population Pharmacoepigenomics
- Population Variations of Epigenetic Patterns and Population Pharmacoepigenomics
- Human Epigenome Projects and Population Pharmacoepigenomics
- Population Pharmacoepigenomics in Relation to Pharmacokinetics
- Population Pharmacoepigenomics in Relation to Pharmacodynamics
- 3D and 4D Chromatin Structures in the Nuclei of Cells in the Liver and Other Body Organs and Population Pharmacoepigenomics
- Population Pharmacoepigenomics in Relation to Adverse Drug Reactions and Drug Interactions
- Conclusions
- Population Pharmacoepigenomics Case Study
- Abbreviations
- References
- Section VIII: Epigenetics and Human Disease
- Chapter 35. Cancer Epigenetics
- Abstract
- Outline
- Introduction
- Epigenetic Influences Over a Lifetime and Cancer Risk
- Epigenetics in Cancer: Remodelers, Writers, Readers, and Erasers
- Genetic and Epigenetic Classification of Cancer
- Epigenetic Biomarkers in Cancer
- Epigenetics as Cancer Therapeutic Targets
- Future Perspectives
- Abbreviations
- References
- Chapter 36. The Role of Epigenetics in Autoimmune Disorders
- Abstract
- Outline
- Epigenetic Mechanisms Influence Autoimmune Processes
- Mechanisms of Autoimmunity
- Epigenetics of Immune Cells
- Epigenetics of Systemic Lupus Erythematosus
- Epigenetics of Rheumatoid Arthritis
- Multiple Sclerosis
- Type 1 Diabetes Mellitus
- Systemic Sclerosis
- Use of Epigenetic Modifications as Potential Biomarkers
- Use of Epigenetic Modifiers for Potential Diagnosis and Therapy in Autoimmune Diseases
- Summary
- Multiomics and machine learning accurately predict clinical response to adalimumab and etanercept therapy in patients with rheumatoid arthritis [ex: Autoimmunity Epigenetics Case Study]
- Abbreviations
- References
- Chapter 37. Epigenetics of Brain Disorders
- Abstract
- Outline
- Introduction
- Important Epigenetic Mechanisms for the Brain
- Epigenetic Dysregulation in Neurodevelopmental Disorders: The Example of Rett Syndrome
- Epigenetic Dysregulation in Neurodegenerative Disorders: The Example of Alzheimer’s Disease
- Epigenetic Dysregulation in Psychiatric Disorders: The Example of Depression
- Epigenetic Dysregulation by Environmental Stress: The Example of Early-life Stress
- Conclusions and Outlook
- Summary
- Research case study
- Acknowledgments
- References
- Chapter 38. Epigenetics of Metabolic Diseases
- Abstract
- Outline
- Introduction
- Impact of Age and Lifestyle Factors on the Epigenome
- Epigenetic Memory, Prenatal Exposure, and Risk of Metabolic Disease
- Epigenetic Features of Metabolic Diseases
- Conclusions
- Abbreviations
- References
- Chapter 39. Imprinting Disorders in Humans
- Abstract
- Outline
- Introduction
- Clinical Findings in Imprinting Disorders
- Molecular Findings in Imprinting Disorders
- Causes of Disturbed Imprinting
- Cis-acting Factors
- Trans-acting Factors
- Maternal Effect Mutations and Multilocus Imprinting Disturbance
- Translational Use of New Findings in ImpDis and New Methodologies
- Genetic and Reproductive Counseling
- Clinical Management
- Concluding Remarks
- References
- Section IX: Epigenetic Therapy
- Chapter 40. Clinical Applications of Histone Deacetylase Inhibitors
- Abstract
- Outline
- Introduction
- HDACi for the Treatment of Hematological Malignancies
- HDACi in the Treatment of Solid Tumors
- Clinical Applications of HDACi for Noncancer Diseases
- Conclusions and the Future Directions of the Clinical Applications of HDACi
- References
- Chapter 41. Combination Epigenetic Therapy
- Abstract
- Outline
- Introduction
- Chromatin-remodeling Agents, Combined Treatment, and Targeted Therapy
- DNA Methylation/Demethylation and Combined Treatment
- Histone Modifications and Histone-modifying Enzymes for Epigenetic Treatment
- Conclusions and Future Perspectives
- Clinical Trial
- References
- Section X: The Future of Epigenetics
- Chapter 42. New Directions for Epigenetics: Application of Engineered DNA-binding Molecules to Locus-specific Epigenetic Research
- Abstract
- Outline
- Introduction
- General Information on Engineered DNA-binding Molecules
- Locus-specific Epigenome Editing
- Locus-specific Identification of Epigenetic Molecules that Interact with Target Genomic Regions
- Conclusions
- References
- Index
- No. of pages: 918
- Language: English
- Published: September 8, 2022
- Imprint: Academic Press
- Hardback ISBN: 9780323919098
- eBook ISBN: 9780323919500
TO
Trygve O Tollefsbol
Dr. Tollefsbol is a Distinguished Professor of Biology and a Senior Scientist in the O’Neal Comprehensive Cancer Center, Integrative Center for Aging Research, Nutrition Obesity Research Center, University Wide Microbiome Center, and the Comprehensive Diabetes Center at the University of Alabama at Birmingham (UAB). He is Director of the UAB Cell Senescence Culture Facility which he established in 1999. Dr. Tollefsbol trained as a Postdoctoral Fellow and Assistant Research Professor with members of the National Academy of Science at Duke University and the University of North Carolina. He earned doctorates in molecular biology and osteopathic medicine from the University of North Texas Health Sciences Center and his bachelor’s degree in Biology from the University of Houston. He has received prior funding from the NCI, NHLBI, NIMH and other federal institutes as well as the Glenn Foundation for Medical Research, Susan G. Komen for the Cure, the American Federation for Aging Research (AFAR), and the American Institute for Cancer Research (AICR) among many other sources.
Affiliations and expertise
Distinguished Professor of Biology, University of Alabama at Birmingham, AL, USA