DNA Modifications in the Brain

DNA Modifications in the Brain: Neuroepigenetic Regulation of Gene Expression begins with an historical overview of the early discoveries surrounding DNA methylation in the mammalian brain and then explores the evidence supporting a role for this epigenetic mechanism in controlling gene expression programs across the lifespan in both normal and diseased states.

Chapters describe new directions and technological advances, and provide an overview of what the future holds for this exciting new field. This book is ideal for medical, graduate and advanced undergraduate students, but is also a great resource for researchers who need a broad introduction to the dynamic nature of DNA that sheds light on evolving concepts of gene-environment interaction and their effects on adaptation and neuropsychiatric disease.

• Provides a comprehensive overview of the many facets of DNA modifications
• Discusses the impact of this dynamic epigenetic mechanism across brain development and lifespan at behavioral, cognitive, molecular and genetic levels
• Contains contributions by influential leaders in the field
• Edited by a Neuroscientist to further promote synthesis between epigenetics, neuroscience, and clinical relevance

Graduate students and post-doctoral fellows in neuroscience and the biomedical sciences; researchers and clinicians

• List of Contributors
• Preface
• Chapter 1. History and Modern View on DNA Modifications in the Brain
  • Introduction
  • DNA Methylation and Its Influence on DNA Structure and Interaction With Proteins
  • Replicative DNA Methylation and the Inheritance of the DNA Methylation Pattern
  • DNA Methyltransferases
  • DNA Demethylation
  • Specificity of DNA Methylation
  • Functional Roles of DNA Methylation
  • Conclusion
• Chapter 2. Approaches to Detecting DNA Base Modification in the Brain
  • Methods for Detection of DNA Modifications in the Genome
  • Bisulfite Sequencing for the Detection of 5mC
  • Analysis of Bisulfite-Treated DNA Without Sequencing
  • Extending Bisulfite Sequencing: Beyond 5mC
  • Restriction Enzymes for DNA Modifications
  • DNA Immunoprecipitation
  • Other Chemical Approaches
  • Summary
  • Detection of DNA Modifications in the Brain
  • Candidate Gene Approach
  • Microarray Screening
  • Genome-Wide Sequencing Approaches
  • Conclusions and Future Directions
• Chapter 3. Active DNA Demethylation in Neurodevelopment
  • Introduction
  • Fundamental Brain Development
  • Interplay of DNA Methylation and Demethylation
  • Mapping and Quantification of the Derivatives of 5mC
  • Discussion
• Chapter 4. TET and 5hmC in Neurodevelopment and the Adult Brain
  • Introduction
  • Global 5hmC and Tet Expression Throughout the Adult Brain
  • Genomic Distribution of 5hmC
  • Role of 5hmC in Brain Development
  • 5hmC Changes Associated With Neuronal Differentiation
  • Role of 5hmC in Aging and Neurodegeneration
  • Role of Tet Enzymes in Brain Function
  • Tet1
  • Tet2
  • Tet3
  • Conclusion
• Chapter 5. Beyond mCG: DNA Methylation in Noncanonical Sequence Context
  • Introduction: Beyond CG Methylation
  • Variable Non–CG Methylation Across Cell Types
  • Non–CG Methylation and Brain Cell Diversity
  • Non–CG Methylation in X Chromosome Inactivation
  • Possible Functions of Non–CG Methylation
  • Outlook and Future Directions
• Chapter 6. DNA Modifications and Memory
  • Introduction
  • DNA Modifications and Neuronal Memory
  • DNA Modification and Behavioral Memory
  • Future Directions
  • Conclusions
• Chapter 7. Measuring CpG Methylation by SMRT Sequencing
  • DNA Methylome of Disease-Associated Repeats
  • Traditional Methods for Observing DNA Methylome
  • SMRT Sequencing to Detect DNA Modifications
  • Prediction of the Regional Methylation State From Kinetic Data
  • Genome-Wide Methylation Pattern of Repetitive Elements in the Human Genome
  • Analysis of an Active Transposable Element
  • Discussion
• Chapter 8. Epigenetic Modifications of DNA and Drug Addiction
  • Introduction
  • Addiction and Reward Pathway
  • DNA Methylation and Its Catalyzing DNMT Enzymes in Addiction
  • Methyl-Cytosine Oxidation and Its TET Catalyzing Enzymes in Addiction
  • Genome-Wide Mapping of DNA Modifications in Addiction
  • Challenges and Future Directions
• Chapter 9. What Does the Future Hold for the Study of Nucleic Acid Modifications in the Brain?
  • Expanding the Realm of Possibility: DNA Modifications on all Four Bases
  • DNA Modifications Drive DNA Structure and Function
  • DNA Modifications Influence DNA Editing
  • Taking Neuroepigenetics to the Next Level: Epitranscriptomics Comes of Age
  • Outstanding Questions and Emerging Technologies
  • Summary and Conclusions
• Index