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 and Expression 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.
During the past few decades we have witnessed an era of remarkable growth in the field of molecular biology. In 1950 very little was known of the chemical constitution of biological systems, the manner in which in formation was transmitted from one organism to another, or the extent to which the chemical basis of life is unified. The picture today is dramati cally different. We have an almost bewildering variety of information detailing many different aspects of life at the molecular level. These great advances have brought with them some breath-taking insights into the molecular mechanisms used by nature for replicating, distributing and modifying biological information. We have learned a great deal about the chemical and physical nature of the macromolecular nucleic acids and proteins, and the manner in which carbohydrates, lipids and smaller mole cules work together to provide the molecular setting of living systems. It might be said that these few decades have replaced a near vacuum of information with a very large surplus. It is in the context of this flood of information that this series of mono graphs on molecular biology has been organized. The idea is to bring together in one place, between the covers of one book, a concise assess ment of the state of the subject in a well-defined field.
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