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Foreword; Contents; DNA and Histone Methylation in Epigenetics; 1 Introduction; 2 DNA Methylation; 2.1 DNA Methylation in Mammals; 2.2 DNA Methyltransferase; 2.3 Methylated DNA Binding Protein; 2.4 Function of DNA Methylation; 3 Histone Methylation; 3.1 Methylation Sites; 3.2 Histone Methyltransferases; 3.3 Methylated Histone Binding Protein; 3.4 Function of Histone Methylation; 4 Perspective; References; Part I: DNA Methylation and Cancer; The Molecular Basis of DNA Methylation; 1 Introduction; 2 DNA Methylation and Gene Silencing; 3 DNA Methyltransferases in Mammals
3.1 Proposed Mechanism of Methylation Reaction3.2 Establishment of DNA Methylation Patterns; 3.2.1 Properties of the de novo Methyltransferases Dnmt3a and 3b; 3.2.2 Structural Properties of Dnmt3; 3.2.3 Sequence Specificity of de novo Methyltransferases; 3.2.4 Factors that Guide Dnmt3 to Target Sites for Methylation; 3.2.5 Function of Dnmt3L in Establishing DNA Methylation Patterns; 3.2.6 Chromatin Structure and Establishment of DNA Methylation; 3.3 Maintenance DNA Methylation; 3.3.1 Structure and Properties of Dnmt1; 3.3.2 Factors Necessary for Maintenance DNA Methylation
3.3.3 Exceptional Expression of Dnmt1 and Its Localization3.4 Cross-Talk Between de novo- and Maintenance-Type DNA Methyltransferases; 4 Modifications of Dnmts; 5 DNA Methylation and Aging; 6 Inhibitors of Dnmts; 7 DNA Demethylation; 8 Perspective; References; The Molecular Basis of DNA Demethylation; 1 Introduction; 2 DNA Methylation Machinery; 3 Passive and Active DNA Demethylation; 4 TET-Mediated Oxidative DNA Demethylation; 4.1 TET Family Dioxygenases; 4.2 TET-Mediated Iterative Oxidation of 5mC; 4.3 TDG-Mediated Excision of 5fC/5caC
4.4 Replication-Dependent Dilution of 5mC Oxidation Derivatives4.5 Other Potential TET-Initiated Active DNA Demethylation Pathways; 5 Potential TET-Independent Active DNA Demethylation Mechanisms; 6 Regulation of TET-Mediated DNA Demethylation; 6.1 Regulation of TET Expression; 6.2 Regulation of TET Activity by Metabolites and Nutrients; 6.3 Regulation by TET-Interacting Proteins and DNA-Binding Proteins; 7 Concluding Remarks; References; DNA Methylation Changes in Cancer; 1 Introduction; 2 DNA Methylation Machinery; 3 DNA De-methylation; 4 DNA Modification Perturbations in Cancer
5 Discrete Hyper-Methylation Events in Cancer6 Changes to the 5hmC Landscape in Cancer; 7 The Role of the TET Enzymes in Cancer; 8 Indirect Impact of DNA Methylation Reprogramming on Cancer Epigenomes; 9 Future Perspectives; References; Misregulation of DNA Methylation Regulators in Cancer; 1 Introduction; 1.1 Molecular Components of the DNA Epigenetic Pathway: Establishment, Interpretation, and Turnover of DNA Modifications; 1.2 Genome-Wide Variation in DNA Modifications, How They Are Achieved, and Their Functional Interpretation; 2 Cancer: The Result of a Deregulated DNA Methylation Pathway
3.1 Proposed Mechanism of Methylation Reaction3.2 Establishment of DNA Methylation Patterns; 3.2.1 Properties of the de novo Methyltransferases Dnmt3a and 3b; 3.2.2 Structural Properties of Dnmt3; 3.2.3 Sequence Specificity of de novo Methyltransferases; 3.2.4 Factors that Guide Dnmt3 to Target Sites for Methylation; 3.2.5 Function of Dnmt3L in Establishing DNA Methylation Patterns; 3.2.6 Chromatin Structure and Establishment of DNA Methylation; 3.3 Maintenance DNA Methylation; 3.3.1 Structure and Properties of Dnmt1; 3.3.2 Factors Necessary for Maintenance DNA Methylation
3.3.3 Exceptional Expression of Dnmt1 and Its Localization3.4 Cross-Talk Between de novo- and Maintenance-Type DNA Methyltransferases; 4 Modifications of Dnmts; 5 DNA Methylation and Aging; 6 Inhibitors of Dnmts; 7 DNA Demethylation; 8 Perspective; References; The Molecular Basis of DNA Demethylation; 1 Introduction; 2 DNA Methylation Machinery; 3 Passive and Active DNA Demethylation; 4 TET-Mediated Oxidative DNA Demethylation; 4.1 TET Family Dioxygenases; 4.2 TET-Mediated Iterative Oxidation of 5mC; 4.3 TDG-Mediated Excision of 5fC/5caC
4.4 Replication-Dependent Dilution of 5mC Oxidation Derivatives4.5 Other Potential TET-Initiated Active DNA Demethylation Pathways; 5 Potential TET-Independent Active DNA Demethylation Mechanisms; 6 Regulation of TET-Mediated DNA Demethylation; 6.1 Regulation of TET Expression; 6.2 Regulation of TET Activity by Metabolites and Nutrients; 6.3 Regulation by TET-Interacting Proteins and DNA-Binding Proteins; 7 Concluding Remarks; References; DNA Methylation Changes in Cancer; 1 Introduction; 2 DNA Methylation Machinery; 3 DNA De-methylation; 4 DNA Modification Perturbations in Cancer
5 Discrete Hyper-Methylation Events in Cancer6 Changes to the 5hmC Landscape in Cancer; 7 The Role of the TET Enzymes in Cancer; 8 Indirect Impact of DNA Methylation Reprogramming on Cancer Epigenomes; 9 Future Perspectives; References; Misregulation of DNA Methylation Regulators in Cancer; 1 Introduction; 1.1 Molecular Components of the DNA Epigenetic Pathway: Establishment, Interpretation, and Turnover of DNA Modifications; 1.2 Genome-Wide Variation in DNA Modifications, How They Are Achieved, and Their Functional Interpretation; 2 Cancer: The Result of a Deregulated DNA Methylation Pathway