E-Book, Englisch, 502 Seiten
ISBN: 978-0-12-387686-7
Verlag: Elsevier Book Series
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)
* Discusses new discoveries, approaches, and ideas * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields
Autoren/Hrsg.
Weitere Infos & Material
1;Front Cover;1
2;Modifications of Nuclear DNA and its Regulatory Proteins;4
3;Copyright;5
4;Contents;6
5;Contributors;12
6;Preface;14
7;Chapter 1: Introduction-Epiphanies in Epigenetics;16
7.1;I. What is an Epigenetic Code?;17
7.2;II. Inheritance;21
7.3;III. Modularity of Epigenetic Modifiers;22
7.4;Acknowledgments;29
7.5;References;29
8;Section I: Evolution of DNA Methylation;38
8.1;Chapter 2: Natural History of Eukaryotic DNA Methylation Systems;40
8.1.1;I. Introduction;42
8.1.2;II. DNA Methyltransferases;45
8.1.3;III. 5mC Demethylation and Potential DNA Demethylases;68
8.1.4;IV. Further Modifications of 5mC in Eukaryotic DNA;78
8.1.5;V. Domains Involved in Discrimination of Methylated Versus Nonmethylated Cytosines in DNA;84
8.1.6;VI. Domain Architectural Logic of Proteins Related to DNA Methylation;96
8.1.7;VII. Evolutionary Considerations;100
8.1.8;VIII. General Conclusions;103
8.1.9;Acknowledgments;105
8.1.10;Appendix Supplementary Material;105
8.1.11;Note Added in Proof;105
8.1.12;References;105
8.2;Chapter 3: Natural History of the Eukaryotic Chromatin Protein Methylation System;120
8.2.1;I. Introduction;122
8.2.2;II. The Categories of Protein Methylases and Their Role in Chromatin Protein Methylation;126
8.2.3;III. Enzymatic Mechanisms That Preempt or Reverse the Action of Protein Methylases in Chromatin;148
8.2.4;IV. Domains Involved in Discrimination of Methylated Peptides;162
8.2.5;V. Domain Architectures of Enzymes in the Chromatin Protein Methylation Network;169
8.2.6;VI. Evolutionary Considerations;174
8.2.7;VII. General Conclusions;177
8.2.8;Acknowledgments;178
8.2.9;Supplementary Information;178
8.2.10;References;178
8.3;Chapter 4: DNA Methylation in Drosophila-A Critical Evaluation;192
8.3.1;I. Evidence for 5-Methyl Cytosine in Drosophila;193
8.3.2;II. Evidence for DNA Methylation Activity of Dnmt2 Enzymes;195
8.3.3;III. Methylation of tRNA by Dnmt2;197
8.3.4;IV. Biological Function of Dnmt2 in Drosophila;199
8.3.5;V. Dinucleotide Abundances in "Dnmt2-only" Organisms: A Hint of DNA Methylation?;200
8.3.6;VI. Methyl-Binding Proteins in Drosophila-Evidence, Concepts, and Inconsistencies;202
8.3.7;Acknowledgment;203
8.3.8;References;203
8.4;Chapter 5: DNA Methylation in Zebrafish;208
8.4.1;I. Introduction;209
8.4.2;II. Methylation Profile of the Zebrafish Genome;210
8.4.3;III. The Zebrafish Methylation Machinery;212
8.4.4;IV. Link Between DNA and Histone Modification in Zebrafish;222
8.4.5;V. DNA Methylation Dynamics in Early Development;223
8.4.6;VI. Evidence for Active DNA Demethylation in Zebrafish;224
8.4.7;VII. Perspectives and Future Directions;226
8.4.8;VIII. Conclusions;228
8.4.9;References;229
9;Section II: Mammalian DNA Methyltransferases - Structure and Function;234
9.1;Chapter 6: Dnmt1: Structure and Function ;236
9.1.1;I. Introduction;237
9.1.2;II. The Functional Domains of Dnmt1 and Dnmt1 Inhibitors;239
9.1.3;III. Structure and Function of Dnmt1 and Its Interaction with Other Molecules;251
9.1.4;IV. New Crystal Structures of Large C-Terminal Fragment of Mouse and Human Dnmt1;258
9.1.5;References;260
9.2;Chapter 7: The DNMT3 Family of Mammalian De Novo DNA Methyltransferases;270
9.2.1;I. Introduction;271
9.2.2;II. Discovery, Primary Structure, and Expression of Mammalian DNMT3A and DNMT3B;272
9.2.3;III. DNMT3A and DNMT3B Drive the Establishment of DNA Methylation Patterns De Novo;274
9.2.4;IV. The DNMT3L Protein, an Essential Accessory Factor for De Novo Methylation;284
9.2.5;V. Interactions Between the De Novo DNA Methylation Machinery and Chromatin;289
9.2.6;VI. Concluding Remarks and Outstanding Questions;292
9.2.7;Acknowledgments;292
9.2.8;References;292
10;Section III: DNA Methylation and Demethylation;302
10.1;Chapter 8 Recruitment of Dnmt1: Roles ofthe SRA Protein Np95 (Uhrf1)and Other Factors;304
10.1.1;I. Roles for DNA Methylation in Transcriptional Regulation and Development;305
10.1.2;II. Maintenance and De Novo DNA Methyltransferases: Two Modes of Action;306
10.1.3;III. Localization of Dnmt1 into Hemimethylated DNA: Search for Recruiter Molecule(s);307
10.1.4;IV. Np95 Is a Cell Cycle-Associated Protein That Localizes to the RF During S-Phase;308
10.1.5;V. Np95 Protein Domains: SRA and More;309
10.1.6;VI. Np95 Recruits Dnmt1 into Hemimethylated Sites During DNA Replication;311
10.1.7;VII. Np95 Is Required for Global DNA Methylation;313
10.1.8;VIII. Other Factors That Recruit/Interact with Dnmt1;314
10.1.9;IX. Concluding Remarks and Future Directions;320
10.1.10;References;322
10.2;Chapter 9: Regulation of Expression and Activity of DNA (Cytosine-5) Methyltransferases in Mammalian Cells;326
10.2.1;I. Transcriptional and Posttranscriptional Regulation of DNMTs;327
10.2.2;II. Regulation of DNMTs by Posttranslational Modifications;332
10.2.3;III. Altered Regulation of DNMTs During Disease;335
10.2.4;IV. Drug-Induced Reductions in DNMT Levels;341
10.2.5;V. Concluding Remarks and Future Directions;343
10.2.6;Acknowledgments;344
10.2.7;References;344
10.3;Chapter 10: Mechanistic and Functional Links Between Histone Methylation and DNA Methylation;350
10.3.1;I. Introduction;350
10.3.2;II. An Evolutionarily Conserved Pathway Between H3K9 Methylation and DNA Methylation;352
10.3.3;III. A Role for LSD1 in Coordinating Histone and DNA Methylation?;354
10.3.4;IV. H3K4 Demethylation and Genomic Imprinting;356
10.3.5;V. Concluding Remarks;358
10.3.6;References;359
11;Section IV: DNA Methylation and Silencing;364
11.1;Chapter 11: RNA-Mediated Silencing Mechanisms in Mammalian Cells;366
11.1.1;I. Introduction;367
11.1.2;II. RNA Constitutes a Structural Component of the Mammalian Cell Nucleus;367
11.1.3;III. A Role for RNAs in Regulating Chromatin Modifications and Organization;368
11.1.4;IV. Repression of Ribosomal DNA Repeats by the NoRC Repressor Complex Is Regulated by IGS Noncoding RNAs;379
11.1.5;V. Pervasive Transcription: RNA at Centromeric and Telomeric Chromatin;381
11.1.6;VI. Aspects of the Evolution of Regulatory RNAs;382
11.1.7;VII. Concluding Remarks and Future Directions in RNA Research;384
11.1.8;Acknowledgment;384
11.1.9;References;385
11.2;Chapter 12: Biological Functions of Methyl-CpG-Binding Proteins;392
11.2.1;I. Introduction;393
11.2.2;II. Families of Methyl-CpG-Binding Proteins;394
11.2.3;III. Biological Functions of Methyl-CpG-Binding Proteins;401
11.2.4;IV. Methyl-CpG-Binding Proteins and Human Disease;404
11.2.5;V. Concluding Remarks;406
11.2.6;Acknowledgments;407
11.2.7;References;407
12;Section V: DNA Methylation in Medicine;414
12.1;Chapter 13: Diseases Associated with Genomic Imprinting;416
12.1.1;I. Overview of Genomic Imprinting;417
12.1.2;II. Disorders Associated with Particular Imprinted Genes and Regions;421
12.1.3;III. Psychiatric Disorders and Other Behavioral Effects;437
12.1.4;IV. The Cost of Imprinting;441
12.1.5;V. Conclusions;446
12.1.6;References;446
12.2;Chapter 14: DNA Methylation Changes in Cancer;462
12.2.1;I. Introduction;462
12.2.2;II. Mechanism Underlying DNA Methylation Changes in Cancer;463
12.2.3;III. The Roles of DNA Methylation in Cancer Signaling Pathways;464
12.2.4;IV. Genetic and Epigenetic Interaction in Cancer;466
12.2.5;V. Hypomethylation in Cancer;466
12.2.6;VI. Epigenetic Therapy;468
12.2.7;VII. Conclusions and Future Directions;469
12.2.8;Acknowledgments;469
12.2.9;References;469
12.3;Chapter 15: Genome-Wide Distribution of DNA Methylation at Single-Nucleotide Resolution;474
12.3.1;I. Impact of Single-Nucleotide-Based Detection on DNA Methylome Profiling;475
12.3.2;II. Overview of Molecular Approaches Used for Methylation Studies;476
12.3.3;III. DNA Methylation Patterns at Single-Nucleotide Resolution;485
12.3.4;IV. DNA Methylation, Histone Modifications, and Other Epigenetic Regulation;487
12.3.5;V. Detection of the 6th Base (5-Hydroxymethylcytosine) and Future Perspectives;488
12.3.6;VI. Concluding Remarks;488
12.3.7;References;489
13;Index;494
14;Colour Plate;504
