Molecular Biology of DNA Methylation

1. Introduction.- 1.1 Introducing DNA Methylation.- 1.2 Methyl Bases in DNA.- 1.3 Distribution of Methylated Bases.- 2. DNA Methylation in the Cell.- 2.1 The Synthetic Reaction.- 2.2a Timing of Methylation in Prokaryotes.- 2.2b Timing of Methylation in Eukaryotes.- 2.3 De Novo and Maintenance Methylation.- 2.4 Demethylation.- 2.5 Methylation in Isolated Nuclei.- 3. DNA Structure and the Effect of Methylation.- 3.1 Structure of DNA.- 3.2 Z-DNA and Supercoiling.- 3.3 Cytosine Methylation and Z-DNA in Vivo.- 3.4 Z-DNA in Vertebrates.- 3.5 Othc. Effects of Cytosine Methylation on DNA Structure.- 3.6 Effect of Adenine Methylation on DNA Structure.- 4. S-Adenosyl-L-methionine—Donor of Methyl Groups.- 4.1 Intracellular Role and Metabolic Cost.- 4.2 Biosynthesis.- 4.3 Adenosyltransferase and Regulation of Intracellular Concentration.- 4.4 Stability and Its Significance.- 4.5 Analogues.- 4.6 Catabolism.- 5. The Methylation Machinery: DNA Methyltransferases.- 5.1 Prokaryote Methylases.- 5.2 Mammalian DNA Methyltransferases.- 5.3 DNA Methyltransferases in Other Eukaryotes.- 5.4 Inhibitors of DNA Methylation.- 6. The Function of DNA Methylation in Bacteria and Phage.- 6.1 Restriction Modification.- 6.2 dcm and dam Methylation.- 6.3 Modification in Phage mu.- 7. Methylation in Higher Eukaryotes.- 7.1 The Sequence Methylated.- 7.2 Deamination of Methylcytosine.- 7.3 Location of Methylcytosine in Different Compartments.- 7.4 Methylation and Recombination in Eukaryotes.- 8. Methylation and Its Relationship with Transcription.- 8.1 Tissue Variation in the Overall Level of DNA Methylation.- 8.2 Changes in DNA Methylcytosine Content During Embryonic Development.- 8.3 What Really Is the Evidence for an Inverse Correlation Between Methylation and Gene Expression?.- 8.4 Methylation andExpression of Genes Transferred into Animal Cells.- 9. X-Chromosome Inactivation.- 9.1 The Phenomenon.- 9.2 Two Models to Explain X-Chromosome Inactivation.- 9.3 Differential Levels of Methylcytosine in X-Chromosomes.- 9.4 Gene Transfer Experiments.- 9.5 Reactivation with Azacytidine.- 10. DNA Methylation and Cancer.- 10.1 DNA Damage and Methylation.- 10.2 Carcinogens and DNA Methylation.- 10.3 Changes in DNA Methylation Associated with Tumors and Transformed Cells.- 11. Variations on a Theme: Patterns of Methylation in Protista, Fungi, Plants, and Animals.- 11.1 Introduction.- 11.2 Protista.- 11.3 Fungi.- 11.4 Animals Excluding Deuterostomia.- 11.5 Plants.- 11.6 Methylation of Organelle DNA.- 12. Has DNA a Role in the Control of Transcription?.- 12.1 The Dilemma.- 12.2 The Relationship Between Undermethylation and Expression.- 12.3 Three Classes of Genes.- 12.4 Ways in Which a Methylation Pattern May Be Established and Changed.- 12.5 The Relevance of Z-DNA Formation to the Study of Gene Expression.- 12.6 A Role in Determination.- 13. Other Possible Functions of Eukaryotic DNA Methylation.- 13.1 Restriction/Modification.- 13.2 Mismatch Repair.- 13.3 Recombination.- 13.4 Biological Clocks.- 13.5 Initiation of DNA Replication.- 13.6 Chromosome Inactivation.- 14. DNA Methylation in Perspective—A Summing Up.- Appendix Methods of Estimation of Minor Bases in DNA.- A.1 Introduction.- A.2 Isolation and Hydrolysis of DNA.- A.3.1 Base Analysis.- A.3.2 Nucleoside and Nucleotide Analysis.- A.4 Use of Antibodies to Methylcytosine.- A.5 Restriction Enzyme Digestion.- A.6 Nearest Neighbor Analysis.- A.7 Maxam-Gilbert Sequencing.- References.