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<b>1 Five Not Four: History and Significance of the Fifth Base</b> (Douglas S Millar, Robin Holliday, and Geoffrey W Grigg). <p>Summary.</p> <p>1.1 Historical Introduction.</p> <p>1.2 Sequencing 5-methylcytosine (5-mC) Residues in Genomic DNA.</p> <p>The Bisulfite Method.</p> <p>1.3 Gene Silencing.</p> <p>1.4 Development.</p> <p>1.5 Abnormal DNA Methylation in Cancer Cells.</p> <p>1.6 Nuclear Transfer.</p> <p>1.7 Aging.</p> <p>1.8 The Future.</p> <p>References.</p> <p><b>2 (Epi)genetic Signals: Towards a Human Genome Sequence of All Five Nucleotides</b> (Walter Doerfler).</p> <p>Summary.</p> <p>2.1 A Linguistic Prologue.</p> <p>2.2 Towards the Complete Sequence of the Human Genome with Five Nucleotides.</p> <p>2.3 Patterns of DNA Methylation – the Scaffold for Building a Functional Genome.</p> <p>2.4 DNA Methylation Patterns in Segments of the Human Genome and in Viral Genomes.</p> <p>2.4.1 On Viral Genomes and Foreign DNA Integrates.</p> <p>2.4.2 DNA Methylation Patterns in the Human Genome.<i>0</i></p> <p>2.5 Ins ertions of Foreign DNA into Established Mammalian Genomes.</p> <p>2.6 <i>De Novo</i> Methylation of Integrated Foreign DNA.</p> <p>2.6.1 Ad12 Genomes in Hamster Tumor Cells.</p> <p>2.6.2 <i>De Novo</i> Methylation of Foreign DNA Integrated into the Mouse Genome by Homologous or Heterologous Recombination [23].</p> <p>2.7 Genome-wide Perturbations in the Mammalian Genome upon Foreign DNA Insertion.</p> <p>2.8 Outlook and Recommendations.</p> <p>References.</p> <p><b>3 Epi Meets Genomics: Technologies for Finding and Reading the 5th Base</b> (Tim Hui-Ming Huang, Christoph Plass, Gangning Liang, and Peter W. Laird).</p> <p>Summary.<i>1</i></p> <p>3.1 The Development of 5th-Base Technologies.</p> <p>3.1.1 Unusual DNA-cutting Enzymes.</p> <p>3.1.2 A Unique Chemical Reaction that Modifies Methylated DNA.</p> <p>3.1.3 The Advance of 5th Base Technologies in Epigenomic Research.</p> <p>3.2 Restriction Landmark Genomic Scanning (RLGS): Finding the 5th-base Signposts in the Genomic Atlas.</p> <p>3.2.1 Principle.</p> <p>3.2.2 How Does RLGS Work?</p> <p>3.2.3 Applications.</p> <p>3.3 Methylation-sensitive Arbitrarily Primed (AP) PCR: Fishing for the 5th Bases in Genomic Ponds.</p> <p>3.3.1 Principle.</p> <p>3.3.2 How Does MS AP-PCR Work?</p> <p>3.3.3 Applications.</p> <p>3.4 Differential Methylation Hybridization (DMH): Identifying the 5th Bases in the Genomic Crossword Puzzle.</p> <p>3.4.1 Principle.</p> <p>3.4.2 How Does DMH Work?</p> <p>3.4.3 Applications.</p> <p>3.5 MethyLight: Finding 5th-base Patterns in Genomic Shadows.</p> <p>3.5.1 Principle.</p> <p>3.5.2 How Does MethyLight Work?</p> <p>3.5.3 Applications.</p> <p>3.6 Exploring the Epigenome.</p> <p>References.</p> <p><b>4 Mammalian Epigenomics: Reprogramming the Genome for Development and Therapy</b> (Wolf Reik and Wendy Dean).</p> <p>Summary.</p> <p>4.1 Introduction.</p> <p>4.2 DNA Methylation.</p> <p>4.3 Histone Modifications.</p> <p>4.4 Imprinting.</p> <p>4.5 Reprogramming and Cloning.</p> <p>4.6 Epimutations and Epigenetic Inheritance.</p> <p>4.7 Epigenomics: The Future.</p> <p>4.7 Conclusions.</p> <p>References.</p> <p><b>5 At the Controls: Genomic Imprinting and the Epigenetic Regulation of Gene Expression</b> (Anne Ferguson-Smith).</p> <p>Summary.</p> <p>5.1 Introduction.</p> <p>5.2 Genomic Imprinting.</p> <p>5.2.1 The Role of DNA Methylation in Imprinted Gene Expression.</p> <p>5.2.3 Organization of Imprinted Genes.</p> <p>5.2.4 The Mechanism of Imprinting at the Mouse <i>Igf2r</i> Imprinted Domain Requires a Cis-acting Noncoding Antisense Transcript Regulated by DNA Methylation (Fig. 5.2a).</p> <p>5.2.5 Imprinting at the Mouse Distal Chromosome 7 Domain Is Regulated by at Least Two Imprinting Control Regions (ICRs) Acting on Different Sets of Genes (Fig. 5.2b & c).</p> <p>5.2.6 The Mechanisms of Imprinting at the PWS/AS Imprinted Domain (Fig. 5.2d).</p> <p>5.3 DNA Methylation and Chromatin.</p> <p>5.4 X Inactivation.</p> <p>5.5 Prospects and Patterns.</p> <p>References.</p> <p><b>6 Epigenetic Trouble: Human Diseases Caused by Epimutations</b> (Jörn Walter and Martina Paulsen).</p> <p>Summary.</p> <p>6.1 Introduction.</p> <p>6.2 Mechanisms of DNA Methylation.</p> <p>6.3 Molecular Recognition of Methylation Patterns.</p> <p>6.4 Rett Syndrome.</p> <p>6.5 ICF Syndrome.</p> <p>6.6 ATR-X Syndrome.</p> <p>6.7 Fragile-X Syndrome.</p> <p>6.8 Imprinting Syndromes.</p> <p>References.</p> <p><b>7 Liver or Broccoli? Food’s Lasting Effect on Genome Methylation</b> (Michael Fenech).</p> <p>Summary.</p> <p>7.1 Introduction.</p> <p>7.2 Important Dietary Sources of Folate, Vitamin B12, Choline, and Methionine.</p> <p>7.3 Evidence from in Vitro Cultures for the Role of Folic Acid in Genomic Stability of Human Cells.</p> <p>7.4 Evidence from in Vivo Studies for the Role of Folate and Vitamin B12 in Genomic Stability of Human Cells.</p> <p>7.5 Environmental and Genetic Factors that Determine the Bioavailability of Folate and Vitamin B12.</p> <p>7.6 Recommended Dietary Allowances (RDAs) for Folate and Vitamin B12 Based on Genomic Stability.</p> <p>7.7 Conclusion.</p> <p>References.</p> <p><b>8 Living Longer: The Aging Epigenome</b> (Jean-Pierre Issa).</p> <p>Summary.</p> <p>8.1 Introduction.</p> <p>8.2 Methylation as a Mark of Epigenetic Silencing.</p> <p>8.3 The Dogma: Formation of Methylation Patterns.</p> <p>8.4 The Reality: Age-related Methylation and Epigenetic Mosaicism in Normal Epithelium.</p> <p>8.5 The Consequences: Methylation and Age-related Diseases.</p> <p>8.6 The Bottom Line: Clinical Implications.</p> <p>References.</p> <p><b>9 Digitizing Molecular Diagnostics: Current and Future Applications of Epigenome Technology</b> (Sven Olek, Sabine Maier, Klaus Olek, and Alexander Olek).</p> <p>Summary.</p> <p>9.1 Introduction.</p> <p>9.2 Molecular Diagnostics.</p> <p>9.2.1 Advantages of Methylation as a Diagnostic Parameter.</p> <p>9.2.2 Cancer Management.</p> <p>9.2.3 Methylation, the Environment, and Lifestyle Diseases.</p> <p>9.2.4 Disease Gene Discovery.</p> <p>9.3 Tissue Engineering.</p> <p>9.3.1 The Development of Tissue Engineering.</p> <p>9.3.2 Complex Result Assessment in Tissue Engineering: an Unmet Need....</p> <p>9.3.3 ...That May Be Met by DNA-methylation Technologies.</p> <p>9.4 Methylation Therapy.</p> <p>9.4.1 Methylation Therapy.</p> <p>9.5 Agriculture.</p> <p>9.6 Outlook.</p> <p>References.</p>

"…eye opening, thought provoking, and well worth reading…highly recommended for everyone." (<i>SIM News</i>, March/April 2004) <p>"...comprehensive...well written...each chapter provides ample information for interested readers." (<i>Quarterly Reviews of Biology</i>, March 2004)</p> <p>"Each chapter provides ample information for interested readers." (<i>New Biological Books</i>, 3/2004)</p> <p>"...an enjoyable and informed treatise...overall, this is a good read..." (<i>The Biochemist</i>, Vol 26(1), Feb 2004)</p> <p>"...an excellent introduction to the unrealized potential of the fifth base in DNA..." (<i>Clinical Chemistry</i>, Vol. 49, No. 9, 2003)</p> <p>"...overall this is a good read..." (<i>The Biochemist Evolution</i>)</p> <p>"...a timely book that addresses an important field in genetics..." (<i>Human Genetics</i>, Vol. 114(121), 2003)</p> <p>"In summary, the book is an excellent introduction to the emerging field of DNA methylation profiling and its relation to human disease, diagnosis, and therapy." (<i>ChemBioChem</i>, 2003)</p>

<p><strong>Stephan Beck</strong> is the editor of <em>The Epigenome: Molecular Hide and Seek</em>, published by Wiley. <p><strong>Alexander Olek</strong> is the editor of <em>The Epigenome: Molecular Hide and Seek</em>, published by Wiley.

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