Epigenetics in Human Disease
- 1st Edition - July 26, 2012
- Editor: Trygve O. Tollefsbol
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 3 8 8 4 1 5 - 2
- eBook ISBN:9 7 8 - 0 - 1 2 - 3 8 8 4 1 6 - 9
Epigenetics is one of the fastest growing fields of sciences, illuminating studies of human diseases by looking beyond genetic make-up and acknowledging that outside factors p… Read more
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Epigenetics is one of the fastest growing fields of sciences, illuminating studies of human diseases by looking beyond genetic make-up and acknowledging that outside factors play a role in gene expression. The goal of this volume is to highlight those diseases or conditions for which we have advanced knowledge of epigenetic factors such as cancer, autoimmune disorders and aging as well as those that are yielding exciting breakthroughs in epigenetics such as diabetes, neurobiological disorders and cardiovascular disease. Where applicable, attempts are made to not only detail the role of epigenetics in the etiology, progression, diagnosis and prognosis of these diseases, but also novel epigenetic approaches to the treatment of these diseases. Chapters are also presented on human imprinting disorders, respiratory diseases, infectious diseases and gynecological and reproductive diseases. Since epigenetics plays a major role in the aging process, advances in the epigenetics of aging are highly relevant to many age-related human diseases. Therefore, this volume closes with chapters on aging epigenetics and breakthroughs that have been made to delay the aging process through epigenetic approaches. With its translational focus, this book will serve as valuable reference for both basic scientists and clinicians alike.
- Comprehensive coverage of fundamental and emergent science and clinical usage
- Side-by-side coverage of the basis of epigenetic diseases and their treatments
- Evaluation of recent epigenetic clinical breakthroughs
Researchers working in basic molecular biology, genetics, and clinical therapy who are interested in either the underlying basis of human diseases or novel means to treat human diseases; advanced undergraduate students, graduate students, university researchers, pharmaceutical company and biotechnology researchers interested in drug development and therapies.
Preface
Contributors
Chapter 1. Epigenetics of Human Disease
1.1 Introduction
1.2 Epigenetic Variation Methods
1.3 Cancer Epigenetics
1.4 Epigenetics of Neurological Disease
1.5 Autoimmunity and Epigenetics
1.6 Human Imprinting Disorders
1.7 Epigenetics of Obesity
1.8 Diabetes: The Epigenetic Connection
1.9 Epigenetics and Allergic Disorders
1.10 Cardiovascular Disease and Epigenetics
1.11 Epigenetics of Human Infectious Diseases
1.12 Reproductive Disorders and Epigenetic Aberrations
1.13 Stem Cell Epigenetics in Human Disease
1.14 Epigenetics of Aging and Age-Associated Diseases
1.15 Conclusion
References
Chapter 2. Methods and Strategies to Determine Epigenetic Variation in Human Disease
2.1 Introduction
2.2 DNA Methylation Analysis
2.3 Histone Modification Analysis
2.4 Non-Coding RNA Analysis: MicroRNA
2.5 Analysis of Genome DNA Replication Program Based on DNA Replication Timing
2.6 Strategy for Epigenomic Investigation Based on Chromosomal Band Structures
2.7 Overview of Recent Epigenetic genome-Wide or Bioinformatic Studies and Strategies
2.8 General Overview and Future Perspective
References
Chapter 3. DNA Methylation Alterations in Human Cancers
3.1 Introduction: Biological Roles of DNA Methylation
3.2 DNA Methylation Alterations in Human Cancers
3.3 Aberrant DNA Methylation in Precancerous Conditions Associated with Chronic Inflammation, Persistent Viral Infection and Smoking
3.4 Abnormal Expression of DNMTs in Human Cancers
3.5 Mutations, Polymorphism and Splicing Alterations of DNMTs and Human Cancers
3.6 Signal Pathways Affecting DNA Methylation Status During Tumorigenesis
3.7 DNA Methylation and Histone Modifications
3.8 Subclassification of Human Cancers Based on DNA Methylation Profiling
3.9 Diagnosis of Cancers in Body Fluids and Biopsy Specimens Based on DNA Methylation Profiles
3.10 Carcinogenetic Risk Estimation Based on DNA Methylation Profiles
3.11 Personalized Medicine Based on DNA Methylation Profiles: Prognostication of Patients with Cancers and Prediction of Response to Chemotherapy
3.12 New Technologies for DNA Methylation Analysis and Future Directions
References
Chapter 4. Alterations of Histone Modifications in Cancer
4.1 Introduction
4.2 Chromatin Organization
4.3 Histone Modifications
4.4 Histone Modifications and Cancer
4.5 Mechanisms Underlying Histone Alterations in Cancer
4.6 Conclusions
References
Chapter 5. MicroRNA in Oncogenesis
5.1 Introduction
5.2 miRNA Biogenesis
5.3 miRNA-Mediated Regulation of Targets
5.4 miRNA and Cancer
5.5 OncomiRs
5.6 Mechanisms of miRNA Deregulation
5.7 miRNA and Treatment Resistance
5.8 Clinical Applications
References
Chapter 6. Epigenetic Approaches to Cancer Therapy
6.1 Introduction
6.2 Histone Acetylation
6.3 Histone Deacetylases
6.4 Histone Methylation and Demethylation
6.5 DNA Methylation
6.6 Acetylation of Non-Histone Proteins
6.7 Future Directions
References
Chapter 7. Epigenomics in Neurobehavioral Diseases
7.1 Introduction
7.2 What is the Epigenome?
7.3 Epigenomic Modulation of Chromatin
7.4 Issues Unique to Neurobehavioral Diseases
7.5 Genetics
7.6 Environment
7.7 Genomic Instability
7.8 Transcriptional Dysregulation
7.9 RNA Epigenomics
7.10 Metabolism
7.11 Nutritional and Drug Interventions
7.12 Putting it all Together
Glossary
Acknowledgments
References
Chapter 8. Emerging Role of Epigenetics in Human Neurodevelopmental Disorders
8.1 Introduction: Few Neurodevelopmental Disorders have Epigenetic Defects
8.2 Components of the Epigenetic Machinery
8.3 Neurodevelopmental Disorders due to Defects in Epigenetic Machinery
8.4 Neurodevelopmental Disorders due to Aberrant Epigenetic Patterns
8.5 Maternal Duplications versus Paternal Duplications in PWS/AS Region
8.6 Conclusions
References
Chapter 9. The Epigenetics of Alzheimer’s Disease
9.1 Alzheimer's Disease
9.2 One-Carbon Metabolism and DNA Methylation in Alzheimer’s Disease
9.3 Histone Tail Modifications and Alzheimer’s Disease
9.4 RNA-Mediated Mechanisms and Alzheimer’s Disease
9.5 Discussion and Conclusions
References
Chapter 10. Epigenetic Modulation of Human Neurobiological Disorders
10.1 Introduction
10.2 Epigenetic Mechanism Associated with Congenital Neurobiological Disorders
10.3 Epigenetic Mechanism Underlying Alteration of the Brain Function by Environmental Factors
10.4 Transgenerational Epigenetic Inheritance (Non-Mendelian Disease Inheritance)
10.5 Epigenetic Medicine for Neurobiological Disorders
10.6 Conclusion
References
Chapter 11. Epigenetic Basis of Autoimmune Disorders in Humans
11.1 Immunity and Autoimmunity
11.2 Epigenetic Deregulation in Autoimmunity
11.3 Conclusions
References
Chapter 12. Approaches to Autoimmune Diseases Using Epigenetic Therapy
12.1 Introduction
12.2 Pathophysiologic Basis for the Development of Epigenetic Treatments in Autoimmunity
12.3 Pathology of Autoimmune Disease and Potential Targets for Epigenetic Drugs
12.4 HDAC Inhibitors
12.5 DNA Methylation and DNA Methyltransferases
12.6 MicroRNA
12.7 Antagomirs
12.8 Techniques to Measure Epigenetic Alterations – Application of Epigenetics as Biomarkers
12.9 Potential Side Effects of Treatment with Epigenetic Drugs in Autoimmune Diseases
12.10 Balancing Conventional Therapy and Epigenetic Therapy
12.11 Where do we go from here?
12.12 Discussion
References
Chapter 13. Epigenetic Mechanisms of Human Imprinting Disorders
13.1 Introduction
13.2 Chromatin Structure Reflects Epigenetic Modifications
13.3 DNA Methylation and Transcriptional Silencing
13.4 Maintenance and Establishment of DNA Methylation During Development
13.5 Genomic Imprinting
13.6 Uniparental Disomy
13.7 Epimutations
13.8 Imprinting Center Mutations
13.9 Mutations in Imprinted Genes
13.10 Copy Number Abnormalities Encompassing Imprinted Genes
13.11 Mutations in Imprinting Establishment or Maintenance Machinery
13.12 Chromosome 6q24
13.13 Chromosome 7
13.14 Chromosome 11p15
13.15 Chromosome 14q32.2
13.16 Chromosome 15q11-q13
13.17 Chromosome 20q13.32
13.18 Hypomethylation at Multiple Imprinted Loci
13.19 Conclusion
References
Chapter 14. Epigenomic Factors in Human Obesity
14.1 Introduction
14.2 Epigenomic Marks
14.3 A Role for Imprinting Abnormalities in Obesity
14.4 Conflict Theory of Imprinting
14.5 Rare Imprinted Abnormalities with Obesity-Related Phenotypes
14.6 Dietary Influence on DNA Methylation in Murine Models
14.7 Obesogenic Environment Effects on Common Human Obesity
14.8 Aging Effect on DNA Methylation
14.9 Developmental Epigenomic Dysregulation
14.10 Fetal Plasticity
14.11 Postnatal Environmental Mismatch
14.12 Hypernutrition
14.13 Epigenetic Analysis of Leptin
14.14 Histone Epigenomic Modifiers – Master Metabolic Regulators
14.15 Metastable Alleles in Human Associated with Obesity
14.16 Parent-of-Origin Genetic Effects
14.17 Epigenomic-Wide Association Studies (EWAS) in Human Obesity
14.18 Future Prospects
References
Chapter 15. Epigenetic Approaches to Control Obesity
15.1 The Changing Epidemiology of Obesity
15.2 Developmental Origins of Obesity
15.3 Animal Studies of Early Development and Metabolic Programming
15.4 Developmental Plasticity
15.5 Epigenetics and Developmental Programming by the Early Life Environment
15.6 Epigenetics and Early-Life Nutrition
15.7 Identification of Predictive Epigenetic Markers of Future Obesity
15.8 Conclusions
References
Chapter 16. Epigenetics of Diabetes in Humans
16.1 Introduction
16.2 Epigenetic Mechanisms
16.3 Epigenetics, Insulin Secretion, and Diabetes
16.4 Epigenetics, Insulin Resistance, and Diabetes
16.5 Prospective
References
Chapter 17. The Potential of Epigenetic Compounds in Treating Diabetes
17.1 The Problem of Diabetes
17.2 Epigenetics
17.3 Aberrant Epigenetic Regulation of Gene Expression or Protein Function as a Cause of Diabetes
17.4 Aberrant Epigenetics within the Diabetic Setting
17.5 Non-Epigenetic Effects of Histone Modifier Proteins with Diabetes Pathogenesis
17.6 Potential for the Use of HDACi to Ameliorate or Treat Symptoms of Diabetes Pathogenesis
17.7 Conclusions
References
Chapter 18. Epigenetic Aberrations in Human Allergic Diseases
18.1 Introduction and Context: The Rising Prevalence of Allergic Diseases
18.2 Mechanisms of Allergic Response
18.3 Fetal life: The Critical Period of Immune Development
18.4 Developmental Differences in Gene Expression in Allergic Disease
18.5 Epigenetic Regulation of Immune Development
18.6 Factors that Modulate Allergic Disease Risk Through Epigenetic Mechanisms
18.7 Conclusions
References
Chapter 19. Therapy of Airway Disease: Epigenetic Potential
19.1 Introduction
19.2 Histone Acetylation and Inflammatory Gene Regulation
19.3 Acetylation of Non-histone Proteins
19.4 Corticosteroids Suppress Inflammation via Epigenetic Mechanisms
19.5 Molecular Mechanisms of Corticosteroid Resistance
19.6 Theophylline as an Epigenetic Modulator
19.7 Other Drugs
19.8 Future Directions
References
Chapter 20. The Role of Epigenetics in Cardiovascular Disease
20.1 Introduction
20.2 Epigenetics and EC Homeostasis
20.3 Epigenetics and SMC Homeostasis
20.4 Epigenetics and Atherosclerosis
20.5 Epigenetics and Heart Failure
20.6 Biomarker and MicroRNA
20.7 Summary and Future Perspectives
Acknowledgments
References
Chapter 21. Epigenetics and Human Infectious Diseases
21.1 Introduction
21.2 Epigenetic Modifications Elicited in Host Cells During Bacterial Infections
21.3 Virus-induced Epigenetic Alterations
21.4 Epigenetic Alterations Elicited in the Host Tissue by Trematode Infections
21.5 Conclusions
References
Chapter 22. The Epigenetics of Endometriosis
22.1 Introduction
22.2 Methods
22.3 All Roads Lead to Epigenetics
22.4 Evidence in Support that Endometriosis is an Epigenetic Disease
22.5 Histone Modifications in Endometriosis: An Unexplored Frontier
22.6 Epigenetic Aberration: Cause or Consequence?
22.7 Therapeutic Implications
22.8 Diagnostic and Prognostic Implications
22.9 Conclusions and Future Research Directions
Acknowledgment
References
Chapter 23. Aberrant DNA Methylation in Endometrial Cancer
23.1 Introduction
23.2 Epigenetic DNA Hypermethylation in Cancer Cells
23.3 Aberrant DNA Methylation in Endometrial Cancer
23.4 Methylation of microRNA in Endometrial Cancer
23.5 Application of Aberrant DNA Hypermethylation to Diagnostics
23.6 Application of Aberrant DNA Hypermethylation to Treatment
23.7 Future Directions and Conclusion
References
Chapter 24. Stem Cell Epigenetics and Human Disease
24.1 Introduction
24.2 Epigenetics
24.3 Stem Cell Epigenetics
24.4 Histone Variants and Exchange of Histones
24.5 Chromatin Bivalency in ESCs
24.6 Changing the Epigenetic Landscape During Cellular Reprogramming
24.7 Stem Cell Epigenetics and Human Disease
24.8 Modeling of Human Epigenetic Disorders Using iPSCs
24.9 Future Studies
References
Chapter 25. Non-Coding RNA Regulatory Networks, Epigenetics, and Programming Stem Cell Renewal and Differentiation: Implications for Stem Cell Therapy
25.1 Major Types of Stem Cells
25.2 A Brief Overview of Epigenetics
25.3 Epigenetic Programming of Stem Cells
25.4 Final Comments
References
Chapter 26. Aging and Disease: The Epigenetic Bridge
26.1 Introduction
26.2 Genes and Aging
26.3 The Dynamic Methylome
26.4 Epigenetic Dynamics in the Aging Brain
26.5 The Complexity of the Age-Associated Epigenetic Changes
26.6 Healthy and Pathological Aging
26.7 Environment, Epigenetics, and Aging
26.8 Epigenetics and Age-Associated Diseases
26.9 One Carbon Metabolism
26.10 One-carbon Metabolism in Aging and Neurodegeneration
26.11 Epigenetics and Neurodegeneration: The Alzheimer’s Disease Paradigm
26.12 Aged AD Mice and Epigenetics
26.13 Conclusion
References
Chapter 27. Early-Life Epigenetic Programming of Human Disease and Aging
27.1 Introduction
27.2 Intrauterine Growth Restriction
27.3 Fetal Macrosomia
27.4 Endocrine Programming During Intrauterine Development
27.5 Intrauterine Growth Restriction and Reprogramming of the Hypothalamic–Pituitary–Adrenal Axis
27.6 Early-life Programming of the Growth Hormone/Insulin-Like Growth Factors Axis
27.7 Early Interventions to Prevent and Treat Endocrine–Metabolic Disturbances
27.8 Early-Life Nutritional Programming of Adult Health and Aging
27.9 The Thrifty Phenotype and Thrifty Epigenotype Concepts
27.10 Prenatal Famine and Adult Health Outcomes
27.11 Effect of Prenatal Exposure to Methyl Donors on Developmental Programming
27.12 Long-Term Programming Effects of Prenatal Stress
27.13 Long-Term Impacts of Maternal Substance Use During Pregnancy
27.14 Programming Effect of Early-Life Exposure to Environmental Toxicants
27.15 Epigenetic Risks of Assisted Reproductive Technologies
27.16 Conclusions and Future Directions
References
Index
Color Plates
- Edition: 1
- Published: July 26, 2012
- Language: English
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, USARead Epigenetics in Human Disease on ScienceDirect