DNA Methylation: Development, Genetic Disease and Cancer (eBook)

Preface 5
List of Contents 7
List of Contributors 9
The Regulation of Chromatin and DNA-Methylation Patterns in Blood Cell Development 10
1 Cell-fate Decisions in the Haematopoietic System 10
2 Transcription Factors Co-operate with Chromatin Components and Reorganise Chromatin Structure Prior to the Activation of Gene Expression 12
3 The Role of Transcription Factors and Chromatin Components in the Regulation of Cell- fate Decisions 16
4 Outlook: Epigenetic Plasticity and Reprogramming 18
References 19
Methylation Dynamics in the Early Mammalian Embryo: Implications of Genome Reprogramming Defects for Development 22
1 Methylation Reprogramming in Early Mouse Embryos 23
2 Species Differences in Methylation Reprogramming 26
3 Methylation Reprogramming Defects 27
References 29
Epigenetic Regulation in Drosophila 32
1 DNA Methylation in Drosophila 33
2 The Dnmt2 Methyltransferase 34
3 DNA Methylation-Dependent Chromatin Structures 35
4 The Methyl-DNA Binding Protein MBD2/3 36
5 A Functional DNA Methylation System in Drosophila 38
6 Chromatin-Based Maintenance of Gene Expression 40
7 Characterization of PcG/TrxG Complexes 41
8 PC-Containing PcG Complexes and the Compaction of Chromatin 42
9 ESC/E(Z)-Containing Complexes and Histone Deacetylation/Methylation 44
10 The Complexity of PcG/TrxG-Regulated Chromatin 45
References 47
Epimutations in Human Disease 54
1 Epigenetic Inheritance 54
2 Classification of Epimutations 56
3 Causes of Primary Epimutations 62
4 Epigenetic Candidate Diseases 64
References 65
Epigenotypes of Latent Herpesvirus Genomes 70
1 Cellular and Viral Epigenotypes 71
2 Epigenetic Modifications of a-Herpesvirus Genomes 73
3 Epigenetic Modifications Regulate the Activity of a ß-Herpesvirus Promoter 75
4 Epigenetic Modifications of Latent .-Herpesvirus Genomes 76
References 83
Epigenetics of Complex Diseases: From General Theory to Laboratory Experiments 90
1 Introduction 91
2 Epigenetics and Complex Disease 92
3 Strategies for Detection of Epigenetic Differences in Complex Genomes 100
4 Study of the Epigenetic Norm 115
References 116
MSL Proteins and the Regulation of Gene Expression 126
1 Introduction 127
2 The DCC of Drosophila melanogaster 128
3 Initiation of Dosage Compensation 129
4 Assembly of the DCC 129
5 Targeting and Distribution of the DCC 130
6 MSL Binding Sites 135
7 Modification of Chromatin by the DCC 137
8 Interpreting the Histone Modifications Placed by the DCC 138
9 Molecular Mechanism of Dosage Compensation 140
10 The Inverse Effect Hypothesis 142
References 143
DNA Methylation Profiles of Female Steroid Hormone- Driven Human Malignancies 150
1 Introduction 151
2 Normal and Aberrant DNA Methylation Profiles 153
3 Gender-Specific Gene Methylation Profiles in Four Hormone- Driven Cancers 156
4 Conclusions 176
References 178
Genome-wide Analysis of DNA Methylation Changes in Human Malignancies 188
1 Introduction 189
2 DNA Methylation and the Genome 189
3 The DNA Methylation Machinery 190
4 DNA Methylation and Gene Silencing 191
5 Aberrant DNA Methylation in Cancer 192
6 Loss of DNA Methylation in Cancer 192
7 Gain of DNA Methylation in Cancer 194
8 Number of Methylated CpG Islands in the Tumor Genome 195
9 Targets for Promoter Hypermethylation 198
10 The Establishment of Tumor Type-Specific and Non-random Aberrant DNA Methylation 198
References 202
Decreased Fidelity in Replicating DNA Methylation Patterns in Cancer Cells Leads to Dense Methylation of a CpG Island 208
1 Introduction 209
2 Fidelity in Normal Mammary Epithelial Cells 210
3 Decreased Fidelity in Gastric Cancer Cells 213
4 Decreased Fidelity and Induction of Dense Methylation 213
5 Molecular Basis for CIMP, and Variation of the Fidelity Among CGIs 216
6 Epilogue 217
References 218
Methylation of Endogenous Human Retroelements in Health and Disease 220
1 Introduction 221
2 Methylation of Retroelements 225
3 Functions of Retroelements in the Human Genome 229
4 Endogenous Retroelements in Acquired Human Diseases 235
5 Retroelement Methylation and Expression in Human Cancer 236
6 Retroelement Methylation and Expression in Human Autoimmune Diseases 243
7 Conclusion: Open Questions 246
References 248
Cancer-Linked DNA Hypomethylation and Its Relationship to Hypermethylation 260
1 Overview 261
2 Background: Tissue-Specific DNA Methylation 261
3 Background: Vertebrate DNA Methylation and Gene Expression 262
4 Background: Vertebrate DNA Methylation and Development 263
5 Global DNA Hypomethylation in Human Cancer 264
6 Hypomethylation of Tandem Repeats in Cancer 265
7 DNA Hypomethylation and Chromosome Rearrangements 266
8 DNA Hypomethylation and Possible trans Effects on Gene Expression 268
9 DNA Hypomethylation vs DNA Hypermethylation in Cancer: Distinct Aspects and Overlaps 270
10 Conclusions 273
References 274
Subject Index 284