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Long-range control of gene expression / edited by Veronica van Heyningen, Robert E. Hill. — Amsterdam ; Oxford : Elsevier Academic Press, 2008. – (58.14/A244/v.61)

Contents

        Contents
    
    Contributors xi
    Preface xiii
    1 Chromatin Structure and the Regulation of Gene Expression: The Lessons of PEV in drosophila
    I. Introduction: Position Effect in Drosophila 2
    II. Historical Background of the PEV Phenotype
    III. Types of PEV 8
    IV. Genome Organization and PEV 19
    V. Concluding Remarks 29
    References 31
    2 Polycomb Group Proteins and Long-Range Gene Regulation 45
    I. Introduction 46
    II. Genetic and Biochemical Characterization of PcG Proteins 48
    III. PcG Mechanisms of Action 49
    IV. PcG Proteins and Long-Range Gene Silencing 53
    V. PcG and Very Long-Range Gene Silencing: "Teleregulation" of Gene Expression 57
    VI. Conclusions and Prospects 61
    References 62
    3. Evolution of Cis-Regulatory Sequences in drosophila 67
    I. Introduction 68
    II. Developmental Homeostasis, Sequence Turnover, and Stabilizing Selection 72
    III. Enhancer Evolution and Loss or Gain of Traits 84
    IV. Cis-Trans Coevolution 91
    V. Evolution of New Regulatory Modules 95
    VI. Conclusions 98
    References 99
    4. β-Globin Regulation and Long-Range Interactions 107
    I. Introduction 108
    II. The fl-Globin Locus 109
    III. Models of Long-Range Control of Gene Expression by Enhancers 115
    IV. Long-Range Activation by the/3-Globin LCR 117
    V. Enhancement of Transcription by the/3-Globin LCR: Rate-Limiting Steps 127
    VI. The Concept of an Active Chromatin Hub 131
    VII. Future Directions 132
    References 133
    5. Long-Range Regulation of α-Globin Gene Expression
    I. Introduction 144
    II. The Normal Structure and Evolution of the α-Globin Cluster 146
    III. Functional Analysis of the α-Globin Regulatory Domain 147
    IV. Structure of the Upstream Regulatory Elements and the Promoters 152
    V. Transcription Factors Involved in Erythropoiesis 153
    VI. Cellular Resources for Studying the Key Stages of Hematopoiesis 157
    VII. Transcription Factor Binding to the Upstream Regulatory Elements 158
    VIII. Transcription Factor Binding to the Promoter 159
    IX. The Recruitment of RNA Polymerase and GTFs to the α-Globin Cluster 160
    X. What Role Do the Remote Regulatory Elements Play ?
    XI. How Do the Upstream Elements Interact with the Promoter? 162
    XII. Sequential Activation of the a-Globin Gene Cluster During Differentiation 165
    XIII. Conclusions, Speculation, and Future Directions 166
    References 169
    6. Global Control Regions and Regulatory Landscapes in Vertebrate Development and Evolution 175
    I. Introduction 176
    II. Global Controls 178
    III. Co-Expression Chromosomal Territories, Regulatory Landscapes, and Global Control Regions 185
    IV. Mechanims of Underlying Global Regulation 188
    V. Co-Expression Chromosomal Territories, Regulatory Landscapes: Bystander Effects or Functional Operons? 192
    VI. Evolutionary Implications of Global Gene Control 195
    VII. Global Regulation, Chromosomal Architecture, and Genetic Disorders 197
    VIII. Concluding Remarks 197
    References 198
    7. Regulation of Imprinting in Clusters: Noncoding RNAs Versus Insulators 207
    I. Introduction 208
    II. Insulator Model of Regulation 209
    III. The ncRNA Model of Regulation 212
    IV. Dlkl/Gtl2 Imprinted Cluster: A Bit of Everything 215
    V. Conclusions 218
    References 219
    8. Genomic Imprinting and Imprinting Defects in Humans 225
    I. Introduction 226
    II. The Mechanisms of Genomic Imprinting 226
    III. Imprinting Defects 230
    IV. Conclusions 242
    References 243
    9. Epigenetic Gene Regulation in Cancer 247
    I. Introduction 248
    II. Cancer Cells Show A Disruption of DNA Methylation Patterns 250
    III. Disruption of the Histone Modification Profile in Cancer 253
    IV. Cascades of Epigenetic Deregulation in Cancer 256
    V. What Are the Mechanisms That Lead to Aberrant Methylation Patterns in Cancer?
    VI. Epigenetic therapy for cancer treatment
    References
    10. Genomic Identification of Regulatory Elements by Evolutionary Sequence Comparison and Functional Analysis 269
    I. Introduction 270
    II. Genomic Architecture of the Human Genome 271
    III. Computational Methods of Predicting Regulatory Elements 276
    IV. In Vivo Validation and Characterization of Transcriptional Regulatory Elements 282
    V. Conclusions 286
    References 287
    11. Regulatory Variation and Evolution: Implications for Disease 295
    I. Introduction 296
    II. Evolution and Variation of Noncoding DNA 297
    III. Natural Selection in Noncoding DNA 300
    IV. Gene Expression Studies 301
    V. Disease Implications 302
    VI. Conclusions 303
    References 304
    12. Organization of Conserved Developmental Regulators Elements Near Key in Vertebrate Genomes 307
    I. Introduction 308
    II. Gene-Regulatory Networks in Development 309
    III. Identification of Evolutionarily Constrained Sequences Using Phylogenetic Footprinting 310
    IV. Searches for Regulatory Elements Using Evolutionary Conservation 310
    V. Takifugu Rubripes: A Compact Model Genome 312
    VI. Identification of Enhancer Elements Through Fish-Mammal Comparisons 313
    VII. Fish-Mammal Conserved Noncoding Elements Are Associated with Vertebrate Development
    VIII. High-Resolution Analysis of the Organization of CNEs Around Key Developmental Regulators
    IX. General Genomic Environment Around CNEs
    X. CNEs Present in Transcripts 319
    XI. CNEs Located Within UTRs 321
    XII. CNEs Are Located Large Putative Target Gene
    XIII. Discussion
    References
    13. Long-Range Gene Control and Genetic Disease 339
    I. From Genetic Disease to Long-Range Gene Regulation 340
    II. Position Effect Revisited 342
    III. Loss of a Positive Regulator 345
    IV. TWIST, POU3F4, PITX2, SOX3, GLI3, and FOXP2 346
    V. The "Bystander" Effect 353
    VI. MAF, SDC2, TGFB2, REEP3, and PLP1 355
    VII. Two Position Effects--Different Outcomes 357
    VIII. Phenotypes Resulting from Position Effects on More than One Gene 362
    IX. Global Control Regions; HOXD, Gremlin, and Limb Malformations 363
    X. FOX Genes and Position Effects 365
    XI. SOX9 and Campomelic Displasia
    XII. Facioscapulohumeral Dystrophy
    XIII. Aberrant Creation of an Illegitimate siRNA Target Site 370
    XIV. Genetic Disease Due to Aberrant Gene Transcription Can Be Caused by Many Different Mechanisms 371
    XV. Concluding Remarks 378
    References 379
    Index 389