Epigenetics in Human Disease

3rd Edition - October 9, 2023
Editor: Trygve O. Tollefsbol
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 2 1 8 1 1 - 8
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 2 1 8 1 2 - 5

Epigenetics in Human Disease, Third Edition examines the diseases and conditions on which we have advanced knowledge of epigenetic mechanisms, such as cancer, autoimmune disorders… Read more

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Epigenetics in Human Disease, Third Edition examines the diseases and conditions on which we have advanced knowledge of epigenetic mechanisms, such as cancer, autoimmune disorders, aging, metabolic disorders, neurobiological disorders and cardiovascular disease. From molecular mechanisms and epigenetic technology to clinical translation of recent research, the nature and applications of the science is presented for those with interests ranging from the fundamental basis of epigenetics to therapeutic interventions for epigenetic-based disorders, with an emphasis throughout on understanding and application of key concepts in new research and clinical practice.

Fully revised and up-to-date, this Third Edition discusses topics of current interest in epigenetic disease research, including stem cell epigenetic therapy, bioinformatic analysis of NGS data, epigenetic mechanisms of imprinting disorders, microRNA in cancer, epigenetic approaches to control obesity, epigenetics and airway disease, and epigenetics in cardiovascular disease. Further sections explore online epigenetic tools and datasets; early-life programming of epigenetics in age-related diseases; the epigenetics of addiction and suicide, and epigenetic approaches to regulating and preventing diabetes, cardiac disease, allergic disorders, Alzheimer’s disease, respiratory diseases, and many other human maladies. In addition, each chapter now includes chapter summaries, definitions, and vibrant imagery and figures to reinforce understanding, as well as step-by-step methods and disease research case studies.

Cover image
Title page
Table of Contents
Translational Epigenetics Series
Copyright
Contributors
Contributors
Preface
Preface
Part 1. Introduction
Chapter 1. An overview of epigenetics of human disease
1.1. Introduction
1.2. Methodology
1.3. Human cancer
1.4. Neurological disease
1.5. Autoimmunity and epigenetics
1.6. Metabolic disorders
1.7. Other disorders/diseases
1.8. Development, aging, and transgenerational effects
1.9. Future research
1.10. Conclusion
Part 2. Methodology
Chapter 2. Profiling histone posttranslational modifications and chromatin-modifying proteins by high-throughput reverse phase protein array
2.1. Introduction
2.2. RPPA platform for detection of histone PTMs and modifying proteins
2.3. Comparison of histone PTM profiles by RPPA and mass spectrometry analyses
2.4. Epigenetic RPPA application—detection of histone PTMs and their modifiers during somatic cell reprogramming
2.5. Perspective and conclusion
Chapter 3. Bioinformatics of epigenetic data generated from next-generation sequencing
3.1. Introduction
3.2. Preprocessing data from next-generation sequencing
3.3. Read alignment
3.4. Profiling genome-wide DNA methylation
3.5. Assessing DNA‒protein interactions via chromatin-ChIP-seq
3.6. Analysis of the small RNA component of the epigenome
3.7. Profiling chromatin accessibility using ATAC-seq
3.8. Chromosome conformation capture
3.9. Predicting transcriptional factor-binding sites with epigenomics data
3.10. Integration of epigenome data
3.11. Summary
Glossary
Part 3. Human cancer
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 alterations of histone modifications in cancer
4.6. Conclusions
Case study
List of abbreviations
Chapter 5. miRNAs as biomarkers breast cancer and their influence on tumor epigenetics
5.1. Introduction
5.2. Molecular profiling—breast cancer heterogeneity
5.3. miRNAs in breast cancer
5.4. miRNAs in determining prognosis
5.5. Potential use of microRNAs for breast cancer therapeutics
5.6. miRNAs in breast cancer epigenetics
5.7. Limitations of miRNA use in bioanalytics
5.8. Conclusion
Chapter 6. Epigenetic biomarkers: Where are we in cancer therapy
6.1. Introduction
6.2. DNA methylation
6.3. Histone modifications
6.4. Nonhistone protein modifications
6.5. MicroRNAs
6.6. Long noncoding RNAs
6.7. Exosomes
6.8. Future directions
6.9. Chapter summary
A case of a phase III clinical trial combining an HDAC inhibitor with steroidal hormonal therapy
Part 4. Neurological disease
Chapter 7. Epigenetics in neurobehavioral disease
7.1. Introduction
7.2. Epigenetic mechanisms in neurobehavioral disease
7.3. Neurotransmitters
7.4. Mood-based disorders
7.5. Addiction
7.6. Psychotic disorders
7.7. Anxiety, fear, and stress disorders
7.8. Sleep and circadian rhythm disorders
7.9. Methodological challenges
7.10. Conclusion
Case study
Chapter 8. Emerging role of epigenetics in human neurodevelopmental disorders
8.1. Neurodevelopmental disorders diagnostic approaches: A historical overview
8.2. Epigenetics in neurodevelopmental disorders
8.3. DNA methylation
8.4. Histone post-translational modifications
8.5. ATP-dependent chromatin remodeling proteins
8.6. Alterations of 3D chromatin structure
8.7. Noncoding RNAs in neurodevelopmental disorders
8.8. Epigenetic therapy
8.9. Rett syndrome gene therapy case study “(Luoni et al., 2020)”
8.10. Conclusions and remarks
Chapter 9. The epigenetics of neurodegenerative diseases
9.1. Introduction: epigenetics and neurodegenerative diseases
9.2. A brief overview of epigenetic mechanisms
9.3. DNA methylation and histone tail modifications in Alzheimer's disease
9.4. DNA methylation and histone tail modifications in Parkinson's disease
9.5. DNA methylation and histone tail modifications in amyotrophic lateral sclerosis
9.6. DNA methylation and histone tail modifications in Huntington's disease
9.7. Mitoepigenetics and neurodegenerative diseases
9.8. Noncoding RNAs and neurodegenerative diseases
9.9. Conclusion
Case study: DNA methylation in familial amyotrophic lateral sclerosis
List of abbreviations
Glossary
Part 5. Autoimmune disease
Chapter 10. Epigenetic basis of autoimmune disorders in humans
10.1. Introduction
10.2. The pathogenesis of autoimmune diseases
10.3. Epigenetic regulation of gene transcription
10.4. Disordered epigenetic mechanisms in rheumatoid arthritis
10.5. Disordered epigenetic mechanisms in systemic lupus erythematosus
10.6. Disordered epigenetic mechanisms in systemic sclerosis
10.7. Disordered epigenetic mechanisms in primary biliary cholangitis
10.8. Disordered epigenetic mechanisms in type 1 diabetes mellitus (T1D)
10.9. Common epigenetic disorders in autoimmune diseases
10.10. Conclusion
List of abbreviations
Chapter 11. Approaches to autoimmune diseases using epigenetic therapy
11.1. Introduction
11.2. DNA methylation
11.3. DNA hydroxymethylation
11.4. Histone modifications
11.5. Noncoding RNAs
11.6. Influencing epigenetic patterns through behavior
11.7. Potential future interventions
11.8. Conclusions
List of abbreviations
Part 6. Metabolic disorders
Chapter 12. Epigenomics and human obesity
12.1. Introduction
12.2. Epigenetics and human obesity
12.3. DNA methylation regulating genomic imprinting
12.4. DNA methylation regulating metastable epialleles
12.5. Genome-scale CpG methylation approaches and human obesity
12.6. CpG methylation as an established obesity risk factor
12.7. Race/ethnic differences in CpG methylation and obesity
12.8. The future
Chapter 13. Transgenerational and early-life nutrition, epigenetics, and prevention of obesity
13.1. Epidemiological perspectives on obesity
13.2. Developmental influences on obesity risk
13.3. Modifiable transgenerational and perinatal influences on childhood obesity
13.4. Perinatal influences on offspring body fat partitioning
13.5. Perinatal gut microbiota development and childhood obesity
13.6. Experimental studies of early development and metabolic programming
13.7. Developmental plasticity
13.8. Parental influences on developmental epigenetic programming
13.9. Identification of predictive epigenetic markers of future obesity
13.10. Conclusions
Chapter 14. Epigenetics of diabetes in humans
14.1. Epigenetics
14.2. Complications of diabetes and epigenetics
14.3. Key points
Author contributions
Conflict of interest
Chapter 15. The potential of epigenetic compounds in treating diabetes
15.1. Introduction
15.2. Bromodomain and extra-terminal bromodomain inhibitors
15.3. Histone deacetylase inhibitors and activators (SIRT [Sirtuin] activators)
15.4. Lysine acetyltransferase inhibitors
15.5. Histone demethylase inhibitors
15.6. miRNA-based therapeutics
15.7. Conclusions
Part 7. Other disorders/diseases
Chapter 16. Epigenetic processes–driven disorders and therapeutics
16.1. What is epigenetics?
16.2. Epigenetics and environment
16.3. Epigenetics in human diseases
16.4. Conclusion
Chapter 17. Epigenetics of allergic diseases: Allergies, eczema, asthma, and allergic rhinitis
17.1. Prevalence of allergic diseases
17.2. Plasticity of allergic diseases
17.3. Time order and the concept of the developmental origins of health and disease
17.4. Allergy and atopy
17.5. Eczema
17.6. Asthma
17.7. Food allergies
17.8. Allergic rhinits
17.9. Epigenetics
17.10. Epigenetic changes and changes in cell composition
17.11. Epigenetics related to atopy and IgE levels
17.12. Epigenetics of eczema
17.13. Epigenetics of food allergies
17.14. Epigenetics of asthma
17.15. Epigenetics related to allergic rhinitis
17.16. Putting it all together
List of abbreviations
Chapter 18. Nutrient intake, epigenetics, and asthma
18.1. Introduction
18.2. Discussion
18.3. Conclusion
Highlights
Chapter 19. The role of epigenetics in cardiovascular disease
19.1. Introduction
19.2. Etiology and pathobiology of cardiovascular diseases
19.3. DNA methylation and cardiovascular diseases
19.4. The histone code and cardiovascular diseases
19.5. ncRNAs and cardiovascular diseases
19.6. Conclusions
Key points
List of abbreviations
Chapter 20. Therapeutic potential of epigenetic drugs
20.1. Introduction
20.2. Epigenetic regulation in cardiovascular diseases and potential epigenetic drugs
20.3. Exercise
20.4. Clinical trials of epigenetic drugs and outcomes
20.5. Conclusions
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
List of abbreviations
Chapter 22. Therapy of infectious diseases using epigenetic approaches
22.1. Introduction
22.2. Epigenetic modifications
22.3. Posttranscriptional RNA methylation
22.4. Posttranscriptional RNA pseudouridylation
22.5. Epigenetic regulations and infection
22.6. Epigenetic drugs and their applications during infection
22.7. Future perspective of epigenetic modifiers in clinical treatment
22.8. Conclusion
List of abbreviations
Chapter 23. Translational aspects of the endometriosis epigenome
23.1. Introduction
23.2. Epigenetics mechanisms underlying endometriosis
23.3. Translational aspects of the endometriosis epigenome
23.4. Summary
List of abbreviations
Chapter 24. Aberrant DNA methylation signatures in gynecological malignancies: Implications for early diagnosis, prognosis, and therapy
24.1. Introduction
24.2. Epigenetics behind gynecological malignancy
24.3. Analysis of altered DNA methylation profile in different types of gynecological cancer
24.4. Biological implications of DNA demethylation in the landscape of gynecological cancer
24.5. Role of potent microRNAs and lncRNA signatures as diagnostic biomarker in women's reproductive system linked malignancies
24.6. Applications of DNA methylation–based biomarkers in clinics
24.7. Liquid biopsy–based detection of gynecological cancers in clinical practice
24.8. Concluding remarks and future perspectives
Chapter 25. Epigenetics in human reproduction and gynecologic diseases
25.1. Introduction
25.2. Basic concepts of epigenetics
25.3. Gametogenesis
25.4. Embryogenesis
25.5. Infertility
25.6. Role in assisted reproductive technologies
25.7. Transgenerational inheritance
25.8. Epigenetics in gynecologic diseases
25.9. Epigenetics and the prospects for future treatment
25.10. Conclusion
Chapter key points
Human reproduction epigenetics case study
Part 8. Development, aging, and transgenerational effects
Chapter 26. Epigenetics of transgenerational inheritance of disease
26.1. Introduction
26.2. Defining epigenetic inheritance
26.3. Multigenerational inheritance of human disease
26.4. Environmental stressors potentially leading to epigenetic inheritance in humans
26.5. Potential mechanisms of epigenetic inheritance in humans
26.6. Developing a mechanistic understanding of epigenetic inheritance
26.7. Mechanistic candidates of transgenerational epigenetic inheritance
26.8. The classic mammalian example: Agouti viable yellow
26.9. The bandwidth of inheritance
26.10. The importance of the repetitive genome
26.11. Tracking phenotypes and epimutations over multiple generations
26.12. Allowing for phenotypic and epigenetic variability
26.13. Considering genetic effects
26.14. RNA-mediated inheritance of phenotype
26.15. Interactions between epigenetic mechanisms
26.16. Potential adaptive benefits of transgenerational epigenetic inheritance
26.17. Mechanistic extrapolation to human populations
26.18. Conclusions
List of abbreviations
Glossary
Chapter 27. Epigenomic mechanisms and episignature biomarkers in rare diseases
27.1. Introduction
27.2. DNA and chromatin modifications
27.3. Epigenetically regulated monoallelic gene expression: imprinting diseases
27.4. Epigenetically regulated monoallelic gene expression: X-linked diseases
27.5. Epigenetic involvements in trinucleotide repeat diseases
27.6. Diseases of the epigenomic machinery defects
27.7. Interaction of genetic and epigenetic variations in human disease
27.8. Epigenomic involvement in multifactorial neurodevelopmental conditions
27.9. Identification of episignatures in neurodevelopmental disorders
27.10. Mapping episignatures and multiclass classifier development
27.11. Episignatures as a diagnostic biomarker in neurodevelopmental disorders
27.12. Clinical utilization of epigenomic technologies and the advantages of episignatures
Chapter key points
Case study
Chapter 28. Therapeutic approaches to imprinting diseases
28.1. Introduction
28.2. Chromatin organization
28.3. Epigenome editors and genomic basis of imprinting regions
28.4. Gene therapies: Additive gene therapy and CRISPR/Cas9 epi-edition
28.5. Insights into rare imprinting diseases: Clinical management, novel therapies, and clinical trials
28.6. Conclusions
Key points
List of abbreviations
Authors contributions
Conflict of interest
Chapter 29. Stem cell epigenetics in development and disease
29.1. Introduction
29.2. Chromatin dynamics during embryogenesis
29.3. Epigenetics of embryo-derived pluripotent stem cells
29.4. Epigenetic changes during reprogramming to generate induced pluripotent stem cells
29.5. Germ cell disorders
29.6. Epigenetics in adult stem cells and their relationship with disease
29.7. Conclusion
Chapter 30. Noncoding RNA regulatory networks, epigenetics, and programming stem cell renewal and differentiation: implications for stem cell therapy
30.1. Major types of stem cells
30.2. A brief overview of epigenetics
30.3. Epigenetic programming of stem cells
30.4. Consideration of sex as a key biological variable in stem cell therapies targeting noncoding RNA networks
30.5. Final comments
Chapter key points
miRNAs in stem cell therapy for ischemic stroke
Chapter 31. Aging and disease: the epigenetic bridge
31.1. Introduction
31.2. Genes and aging
31.3. The dynamic methylome
31.4. Healthy and pathological aging
31.5. One-carbon metabolism
31.6. Epigenetics and neurodegeneration: the Alzheimer's disease paradigm
31.7. Conclusion
List of abbreviations
Chapter 32. Epigenetic programming of human disease and aging
32.1. Introduction
32.2. Aging epigenetics and cancer
32.3. Epigenetics and neurodegenerative diseases
32.4. Psychiatric diseases
32.5. Cardiovascular diseases
32.6. Diabetes mellitus type 2 and obesity
32.7. Hypertension
32.8. Epigenetics and frailty
32.9. Conclusions
Part 9. Future research
Chapter 33. Epigenetics, epidemiology, and public health
33.1. Introduction
33.2. Epigenetics in disease aetiology
33.3. Epigenetic variation as a biomarker of exposure
33.4. Epigenetic variation as a biomarker of disease
33.5. Epigenetics in disease treatment
33.6. Considerations regarding the implementation of epigenetic epidemiological studies
33.7. Challenges
33.8. Summary
List of abbreviations
Index for Volume 1
Index for Volume 2

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

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Epigenetics in Human Disease

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Trygve O. Tollefsbol