Toxicoepigenetics : Core Principles and Applications.

Front Cover
Toxicoepigenetics: Core Principles and Applications
Copyright
Contents
Contributors
Editors' Biography
Introduction to the Role of the Epigenome in Health and Disease
Section 1: Histone Modifications and Chromatin Structure
Chapter 1-1: Role of Histone Acetylation and Acetyltransferases in Gene Regulation
Introduction
History and Overview
Nucleosome Assembly
Chromatin Folding
Gene Expression
DNA Damage Repair
Toxicoepigenetic Relevance
Histone Acetyltransferases
Families and Structures
Regulation of HATs
Transcriptional Activation
HAT Complexes
SAGA Transcription Regulatory Complex
NuA4 Transcription Regulatory Complex
Elongator Complex
Chromatin Remodeling Complexes
Global Histone Acetylation
Role of Histone Acetyltransferases in Gene Activation
Recruitment of Transcriptional Machinery
Active Genes
Inducible/Repressed Genes
Environmental Exposure
Histone Deacetylases
Families
Catalytic Mechanisms and Structures
Regulation of HDAC Activity
Role of HDACs at Active Genes
Deacetylation and Gene Repression
HDAC Complexes
Conclusion and Perspectives
References
Chapter 1-2: The Role of Histone Methylation and Methyltransferases in Gene Regulation
Introduction
Site Specificity of Histone Methylation
Lysine Methylation
H2BK5 Methylation
H3K4 Methylation
H3K9 Methylation
H3K27 Methylation
H3K36 Methylation
H3K79 Methylation
H4K20 Methylation
H4K5 Methylation
Arginine Methylation
Glutamine Methylation
Regulation of Histone Methylation
Posttranscriptional Modifications
Noncoding RNAs
Regulation of Xenobiotic Biotransformation-Related Genes by Histone Methylation
Histone Methylation and Human Diseases
Histone Methylation and Cancer.

Histone Methylation and Neurological Disorders
Histone Methylation and Other Diseases
Histone Methylation and the Toxicity of Chemicals
Heavy Metals
Endocrine Disruptors (EDCs)
Human Genotoxic Chemical Carcinogens From Occupational and Environmental Exposure
Other Xenobiotics
Conclusion
References
Chapter 1-3: Chromatin Accessibility as a Strategy to Detect Changes Associated With Development, Disease, and Exposure a ...
Chromatin Accessibility as a Marker of Cell Lineage
Methods for Determining Chromatin Architecture and Accessibility
DNase I Hypersensitivity Assays
Micrococcal Nuclease Assays
Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE)
Assay for Transposase-Accessible Chromatin (ATAC)
Nucleosome Occupancy and Methylome Sequencing (NOMe-seq)
Single Cell Assays for Determining Chromatin Accessibility in Heterogenous Cell Populations
Chromatin Accessibility and Disease
Understanding How Environmental Factors Influence Chromatin Accessibility
Chromatin Accessibility and Cancer
Chromatin Signature as a Diagnostic and Therapeutic Target in Cancer
References
Further Reading
Chapter 1-4: Implications for Chromatin Biology in Toxicology
Changes in Chromatin Modification States Are Important in Aging and the Developmental Origins of Health and Disease
Mechanisms by Which Toxicant Exposures Alter the Chromatin Landscape
Repressive Histone Marks and Polycomb Group Proteins
Xenoestrogens
Arsenic
COMPASS Complex
Xenoestrogens
Arsenic
The Histone Methyltransferase G9a
Phthalates
Arsenic
Histone Acetylation
Organotins
Phthalates
Dioxin
Lead
Chromium
Arsenic
Applications of Chromatin Biology to Toxicological Studies
Summary
References
Section 2: DNA Methylation.

Chapter 2-1: The Role of DNA Methylation in Gene Regulation
Chapter Overview
Introduction
Mechanisms of DNA Methylation
De Novo DNA Methylation
Maintenance DNA Methylation
DNA Methylation Patterns and the Developing Organism
X-Chromosome Inactivation
Imprinted Genes and Development
Transposable Elements
DNA Methylation as a Regulator of Gene Expression
DNA Methylation in Gene Promoters Affects Transcription Factor Binding and Vice Versa
DNA Methylation Recruits Methyl-CpG Binding Proteins and Remodels Chromatin
DNA Methylation in the Gene Body Impacts Transcription
DNA Demethylation
TET-Mediated Oxidation and Demethylation
Applications of DNA Methylation in Understanding and Treating Disease
Environmental Links to DNA Methylation
DNA Methylation as a Biomarker for Identifying and Understanding Disease
DNA Methylation in Disease Therapy
References
Chapter 2-2: Implications of DNA Methylation in Toxicology
Introduction
Detection of DNA Methylation
Bisulfite Methods of DNA Methylation Detection
Direct Methods of Locus-Specific or Global DNA Methylation Detection
Direct Methods of Genome-Wide DNA Methylation Detection
Principles of DNA Methylation Modification
Conservation of DNA Methylation Dynamics
Diet-Induced Changes to DNA Methylation
Evolutionary Conservation in Diet and DNA Methylation
Background Diet Considerations in Rodents
Caloric Restriction and DNA Methylation
Macronutrient Restriction
Macronutrient Shifts
Micronutrient or Trace Mineral Deficiencies
Pharmaceuticals
Metals
Metals as Toxicants
High Density Metals
Light Metals
Organic Toxicants
Nonchemical Stress
Future Directions
References
Chapter 2-3: DNA Methylation as a Biomarker in Environmental Epidemiology.

Methylomics as a Potential Biomarker for Both Disease and Toxic Exposures
Methylomics of WBCs in Relation to Disease Causation and Toxic Exposures
Methodological Considerations in Methylome-Wide Association Studies
Platforms That Assess Single-Base Resolution Methylation
Array-Based: MethylationEPIC BeadChip (Infinium) Microarray
Next-Generation Sequencing
Preprocessing and Normalization
MethylationEPIC BeadChip (Infinium) Microarray
Bisulfite Sequencing
Addressing Confounding
Inclusion of Technical Replicates
Calculation for Differentially Methylated Sites
Calculation for Differentially Methylated Regions
Methylomics as a Potential Biomarker for Both Disease and Toxic Exposures
Example: Smoking and AHRR Methylation
Example: Air Pollution and DNA Methylation
Example: Biological Aging as Measured by the Epigenetic Clock
Example: VTRNA2-1 as a Metastable Epiallele
Example: Epigenetic Pathway Linking Prenatal Maternal Stress and Wheeze in Children
Conclusion
References
Chapter 2-4: DNA Hydroxymethylation: Implications for Toxicology and Epigenetic Epidemiology
Introduction
Chemistry of DNA Hydroxymethylation
The Sixth-Base of Cytosine
Distribution of 5-hmC in the Genome
Changes in 5-hmC Level During Development
Measurement of 5-hmC
Global 5-hmC Measurement
Locus-Specific 5-hmC Measurement
DNA Immunoprecipitation (DIP)
Enzymatic and Chemical Modifications
Single Molecule Detection
Exposures to Environmental Toxicants/Stressors and Changes in 5-hmC
Heavy Metals
Environmental Estrogens
Air Pollutants
Pesticides
Ionizing Radiation
Lifestyle
Aging
Discussion and Future Directions
Acknowledgments
References
Section 3: Noncoding RNAs
Chapter 3-1: The Role of Noncoding RNAs in Gene Regulation
Introduction.

Overview of Noncoding RNAs
Transfer and Ribosomal RNA
Long Noncoding RNA (lncRNA)
Competitive Endogenous RNA
Long Intervening Noncoding RNA
Enhancer RNA
Short Noncoding RNA
Piwi-Interacting RNA
Small Nuclear RNA
Short Nucleolar RNA
MicroRNA
Short Interfering RNA
MicroRNA Discovery
MicroRNA Biogenesis and Regulation
Pri-miRNA Transcription and Regulation
Pri-miRNA Processing and Nuclear Export
Maturation of miRNA RISC Formation
Regulation of Mature miRNA by ceRNA
Biological Roles of MicroRNA
Gene Target Silencing
Target Degradation Pathway
Translational Repression
miRNA-Mediated Gene Target Upregulation
Enhanced Biological Impact of miRNAs Through Feedback Loops
Positive Feedback Loop
Negative Feedback Loop
Switching Loops
Biofluid-Based Biomarkers and Cell Communication
Concluding Remarks and Future Directions
Acknowledgments
References
Chapter 3-2: miRNAs and lncRNAs as Biomarkers of Toxicant Exposure
Introduction
miRNAs and Toxicological Response to Chemicals
Endocrine Disruptor Chemicals and Altered miRNA Profile
Bisphenol A
Phthalates
Exposure to Metals
Exposure to Particles
Nanoparticles
Cigarette Smoking
lncRNAs and Toxicological Response to Chemicals
Endocrine Disruptor Chemicals and Altered lncRNA Profile
Bisphenol A
Exposure to Metals and lncRNA Expression
Cigarette Smoking and lncRNA Profile
Summary
References
Further Reading
Section 4: Special Considerations in Toxicoepigenetics Research
Chapter 4-1: Germline and Transgenerational Impacts of Toxicant Exposures
Introduction
The Germline
Germline Specification and the Importance of the Epigenetic Repression of Somatic Fates
PGC's Epigenetic Reprogramming: A Critical Period.

Transgenerational Effects Stemming From Environmental Exposures.