Note: Front Cover -- Modifications of Nuclear DNA and its Regulatory Proteins -- Copyright -- Contents -- Contributors -- Preface -- Chapter 1: Introduction-Epiphanies in Epigenetics -- I. What is an Epigenetic Code? -- II. Inheritance -- III. Modularity of Epigenetic Modifiers -- Acknowledgments -- References -- Section I: Evolution of DNA Methylation -- Chapter 2: Natural History of Eukaryotic DNA Methylation Systems -- I. Introduction -- II. DNA Methyltransferases -- III. 5mC Demethylation and Potential DNA Demethylases -- IV. Further Modifications of 5mC in Eukaryotic DNA -- V. Domains Involved in Discrimination of Methylated Versus Nonmethylated Cytosines in DNA -- VI. Domain Architectural Logic of Proteins Related to DNA Methylation -- VII. Evolutionary Considerations -- VIII. General Conclusions -- Acknowledgments -- Appendix Supplementary Material -- Note Added in Proof -- References -- Chapter 3: Natural History of the Eukaryotic Chromatin Protein Methylation System -- I. Introduction -- II. The Categories of Protein Methylases and Their Role in Chromatin Protein Methylation -- III. Enzymatic Mechanisms That Preempt or Reverse the Action of Protein Methylases in Chromatin -- IV. Domains Involved in Discrimination of Methylated Peptides -- V. Domain Architectures of Enzymes in the Chromatin Protein Methylation Network -- VI. Evolutionary Considerations -- VII. General Conclusions -- Acknowledgments -- Supplementary Information -- References -- Chapter 4: DNA Methylation in Drosophila-A Critical Evaluation -- I. Evidence for 5-Methyl Cytosine in Drosophila -- II. Evidence for DNA Methylation Activity of Dnmt2 Enzymes -- III. Methylation of tRNA by Dnmt2 -- IV. Biological Function of Dnmt2 in Drosophila -- V. Dinucleotide Abundances in "Dnmt2-only" Organisms: A Hint of DNA Methylation?. , VI. Methyl-Binding Proteins in Drosophila-Evidence, Concepts, and Inconsistencies -- Acknowledgment -- References -- Chapter 5: DNA Methylation in Zebrafish -- I. Introduction -- II. Methylation Profile of the Zebrafish Genome -- III. The Zebrafish Methylation Machinery -- IV. Link Between DNA and Histone Modification in Zebrafish -- V. DNA Methylation Dynamics in Early Development -- VI. Evidence for Active DNA Demethylation in Zebrafish -- VII. Perspectives and Future Directions -- VIII. Conclusions -- References -- Section II: Mammalian DNA Methyltransferases - Structure and Function -- Chapter 6: Dnmt1: Structure and Function -- I. Introduction -- II. The Functional Domains of Dnmt1 and Dnmt1 Inhibitors -- III. Structure and Function of Dnmt1 and Its Interaction with Other Molecules -- IV. New Crystal Structures of Large C-Terminal Fragment of Mouse and Human Dnmt1 -- References -- Chapter 7: The DNMT3 Family of Mammalian De Novo DNA Methyltransferases -- I. Introduction -- II. Discovery, Primary Structure, and Expression of Mammalian DNMT3A and DNMT3B -- III. DNMT3A and DNMT3B Drive the Establishment of DNA Methylation Patterns De Novo -- IV. The DNMT3L Protein, an Essential Accessory Factor for De Novo Methylation -- V. Interactions Between the De Novo DNA Methylation Machinery and Chromatin -- VI. Concluding Remarks and Outstanding Questions -- Acknowledgments -- References -- Section III: DNA Methylation and Demethylation -- Chapter 8 Recruitment of Dnmt1: Roles ofthe SRA Protein Np95 (Uhrf1)and Other Factors -- I. Roles for DNA Methylation in Transcriptional Regulation and Development -- II. Maintenance and De Novo DNA Methyltransferases: Two Modes of Action -- III. Localization of Dnmt1 into Hemimethylated DNA: Search for Recruiter Molecule(s) -- IV. Np95 Is a Cell Cycle-Associated Protein That Localizes to the RF During S-Phase. , V. Np95 Protein Domains: SRA and More -- VI. Np95 Recruits Dnmt1 into Hemimethylated Sites During DNA Replication -- VII. Np95 Is Required for Global DNA Methylation -- VIII. Other Factors That Recruit/Interact with Dnmt1 -- IX. Concluding Remarks and Future Directions -- References -- Chapter 9: Regulation of Expression and Activity of DNA (Cytosine-5) Methyltransferases in Mammalian Cells -- I. Transcriptional and Posttranscriptional Regulation of DNMTs -- II. Regulation of DNMTs by Posttranslational Modifications -- III. Altered Regulation of DNMTs During Disease -- IV. Drug-Induced Reductions in DNMT Levels -- V. Concluding Remarks and Future Directions -- Acknowledgments -- References -- Chapter 10: Mechanistic and Functional Links Between Histone Methylation and DNA Methylation -- I. Introduction -- II. An Evolutionarily Conserved Pathway Between H3K9 Methylation and DNA Methylation -- III. A Role for LSD1 in Coordinating Histone and DNA Methylation? -- IV. H3K4 Demethylation and Genomic Imprinting -- V. Concluding Remarks -- References -- Section IV: DNA Methylation and Silencing -- Chapter 11: RNA-Mediated Silencing Mechanisms in Mammalian Cells -- I. Introduction -- II. RNA Constitutes a Structural Component of the Mammalian Cell Nucleus -- III. A Role for RNAs in Regulating Chromatin Modifications and Organization -- IV. Repression of Ribosomal DNA Repeats by the NoRC Repressor Complex Is Regulated by IGS Noncoding RNAs -- V. Pervasive Transcription: RNA at Centromeric and Telomeric Chromatin -- VI. Aspects of the Evolution of Regulatory RNAs -- VII. Concluding Remarks and Future Directions in RNA Research -- Acknowledgment -- References -- Chapter 12: Biological Functions of Methyl-CpG-Binding Proteins -- I. Introduction -- II. Families of Methyl-CpG-Binding Proteins -- III. Biological Functions of Methyl-CpG-Binding Proteins. , IV. Methyl-CpG-Binding Proteins and Human Disease -- V. Concluding Remarks -- Acknowledgments -- References -- Section V: DNA Methylation in Medicine -- Chapter 13: Diseases Associated with Genomic Imprinting -- I. Overview of Genomic Imprinting -- II. Disorders Associated with Particular Imprinted Genes and Regions -- III. Psychiatric Disorders and Other Behavioral Effects -- IV. The Cost of Imprinting -- V. Conclusions -- References -- Chapter 14: DNA Methylation Changes in Cancer -- I. Introduction -- II. Mechanism Underlying DNA Methylation Changes in Cancer -- III. The Roles of DNA Methylation in Cancer Signaling Pathways -- IV. Genetic and Epigenetic Interaction in Cancer -- V. Hypomethylation in Cancer -- VI. Epigenetic Therapy -- VII. Conclusions and Future Directions -- Acknowledgments -- References -- Chapter 15: Genome-Wide Distribution of DNA Methylation at Single-Nucleotide Resolution -- I. Impact of Single-Nucleotide-Based Detection on DNA Methylome Profiling -- II. Overview of Molecular Approaches Used for Methylation Studies -- III. DNA Methylation Patterns at Single-Nucleotide Resolution -- IV. DNA Methylation, Histone Modifications, and Other Epigenetic Regulation -- V. Detection of the 6th Base (5-Hydroxymethylcytosine) and Future Perspectives -- VI. Concluding Remarks -- References -- Index -- Colour Plate.