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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