Eukaryotic Transcription Factors (eBook)

Front cover 1
Eukaryotic transcription factors 4
Copyright page 5
Contents 8
List of tables 14
About the author 16
Preface 18
Preface to the fourth edition 20
Preface to the third edition 22
Preface to the second edition 24
Preface to the first edition 26
Acknowledgements 28
CHAPTER 1. DNA SEQUENCES, TRANSCRIPTION FACTORS AND CHROMATIN STRUCTURE 30
1.1. The importance of transcription 30
1.2. Chromatin structure and its remodelling 31
1.2.1. Chromatin structure and gene regulation 31
1.2.2. Chromatin remodelling factors 33
1.2.3. Histone modifications 34
1.3. DNA sequence elements 38
1.3.1. The gene promoter 38
1.3.2. Sequences involved in the basic process of transcription 39
1.3.3. Sequences involved in regulated transcription 40
1.3.4. Sequences which act at a distance 44
1.3.5. Negatively acting DNA sequences 49
1.3.6. Interaction between factors bound at various sites 50
1.4. Conclusions 52
References 53
CHAPTER 2. METHODS FOR STUDYING TRANSCRIPTION FACTORS 58
2.1. Introduction 58
2.2. Methods for studying DNA–protein interactions 58
2.2.1. DNA mobility shift assay 58
2.2.2. DNAseI footprinting assay 62
2.2.3. Methylation interference assay 66
2.2.4. In vivo footprinting assay 67
2.3. Methods for purifying and/or cloning transcription factors 71
2.3.1. Protein purification 71
2.3.2. Gene cloning 75
2.4. Use of cloned genes 80
2.4.1. Domain mapping of transcription factors 80
2.4.2. Determining the DNA binding specificity of an uncharacterized factor 84
2.4.3. Identification of target genes for transcription factors 86
2.5. Conclusions 91
References 92
CHAPTER 3. RNA POLYMERASES AND THE BASAL TRANSCRIPTIONAL COMPLEX 97
3.1. RNA polymerases 97
3.2. The stable transcriptional complex 99
3.3. RNA polymerase I 100
3.4. RNA polymerase III 102
3.5. RNA polymerase II 105
3.5.1. Stepwise assembly of the RNA polymerase II basal transcriptional complex 105
3.5.2. The RNA polymerase holoenzyme 109
3.6. TBP: the universal transcription factor? 110
3.7. Transcriptional elongation 117
3.8. Conclusions 119
References 119
CHAPTER 4. FAMILIES OF DNA BINDING TRANSCRIPTION FACTORS 125
4.1. Introduction 125
4.2. The homeodomain 126
4.2.1. Transcription factors in Drosophila development 126
4.2.2. The homeobox 127
4.2.3. DNA binding by the helix-turn-helix motif in the homeobox 129
4.2.4. Regulation of DNA binding specificity by interactions between different homeobox proteins 137
4.2.5. Homeodomain transcription factors in other organisms 141
4.2.6. POU proteins 143
4.2.7. Pax proteins 153
4.3. The two cysteine two histidine Zinc finger 155
4.3.1. Transcription factors with the two cysteine two histidine finger 155
4.3.2. DNA binding by the two cysteine two histidine finger 157
4.4. The multi-cysteine Zinc finger 160
4.4.1. Nuclear receptors 160
4.4.2. DNA binding by the multi-cysteine zinc finger 162
4.5. The basic DNA binding domain 171
4.5.1. The leucine zipper and the basic DNA binding domain 171
4.5.2. The helix-loop-helix motif and the basic DNA binding domain 176
4.5.3. Dimerization of basic DNA binding domain-containing factors 178
4.6. Other DNA binding motifs 180
4.7. Conclusions 181
References 183
CHAPTER 5. ACTIVATION OF GENE EXPRESSION BY TRANSCRIPTION FACTORS 190
5.1. Activation domains 190
5.2. Nature of activation domains 192
5.2.1. Acidic domains 192
5.2.2. Glutamine-rich domains 195
5.2.3. Proline-rich domains 195
5.2.4. Functional relationship of the different activation domains 196
5.3. Interaction of activation domains with the basal transcriptional complex 197
5.3.1. Activators and the basal transcriptional complex 197
5.3.2. Stimulation of factor binding 199
5.3.3. Stimulation of factor activity 202
5.4. Interaction of activation domains with other regulatory proteins 206
5.4.1. The mediator complex 206
5.4.2. TAFs 209
5.4.3. CBP and other co-activators 216
5.4.4. A multitude of targets for transcriptional activators 222
5.5. Effect of transcriptional activators on chromatin structure 224
5.5.1. Effect of chromatin remodelling factors 224
5.5.2. Effect on histone modification 232
5.5.3. Transcriptional activation by chromatin structure changes and by stimulation of the basal transcriptional complex 236
5.6. Stimulation of transcriptional elongation 241
5.7. Conclusions 246
References 250
CHAPTER 6. REPRESSION OF GENE EXPRESSION BY TRANSCRIPTION FACTORS 258
6.1. Repression of transcription 258
6.2. Indirect repression 259
6.2.1. Inhibition of activator binding by masking of its DNA binding site 259
6.2.2. Inhibition of activator binding by formation of a non-DNA binding complex 264
6.2.3. Quenching of an activator 266
6.2.4. Degradation of an activator 267
6.3. Direct repression 268
6.3.1. Mechanisms of transcriptional repression 268
6.3.2. Direct repression by DNA binding transcription factors 269
6.3.3. Direct repression by factors binding to the basal transcriptional complex 283
6.4. Inhibition by alteration of chromatin structure 287
6.4.1. Effect of repressors on chromatin 287
6.4.2. Small RNAs and transcriptional inhibition 293
6.5. Inhibition of transcriptional elongation 295
6.6. Conclusions 299
References 301
CHAPTER 7. REGULATION OF TRANSCRIPTION FACTOR SYNTHESIS 307
7.1. Transcription factor regulation 307
7.2. Regulated synthesis of transcription factors 307
7.2.1. The MyoD transcription factor 308
7.2.2. Homeobox transcription factors 317
7.3. Mechanisms regulating the synthesis of transcription factors 330
7.3.1. Regulation of transcription 330
7.3.2. Regulation of RNA splicing 333
7.3.3. Regulation of translation 340
7.4. Conclusions 343
References 344
CHAPTER 8. REGULATION OF TRANSCRIPTION FACTOR ACTIVITY 348
8.1. Evidence for the regulated activity of transcription factors 348
8.2. Regulation by protein–ligand binding 350
8.2.1. Examples of regulation by ligand binding 350
8.2.2. The nuclear receptors 353
8.3. Regulation by protein–protein interactions 361
8.3.1. Inhibition of transcription factor activity by protein–protein interaction 361
8.3.2. Activation of transcription factors by protein–protein interaction 371
8.3.3. Alteration of transcription factor function by protein–protein interaction 371
8.4. Regulation by protein modification 373
8.4.1. Transcription factor modification 373
8.4.2. Phosphorylation 373
8.4.3. Acetylation 383
8.4.4. Methylation 384
8.4.5. Ubiquitination and sumoylation 386
8.5. Regulation by protein degradation and processing 394
8.6. Role of regulated activity 398
8.7. Conclusions 400
References 402
CHAPTER 9. TRANSCRIPTION FACTORS AND HUMAN DISEASE 409
9.1. Diseases caused by transcription factor mutations 409
9.2. Cancer 416
9.3. Cellular oncogenes and cancer 418
9.3.1. Fos, Jun and AP1 418
9.3.2. v-erbA and the thyroid hormone receptor 424
9.3.3. The myc oncogene 428
9.3.4. Other oncogenic transcription factors 435
9.4 Anti-oncogenes and cancer 439
9.4.1. Nature of anti-oncogenes 439
9.4.2. p53 440
9.4.3. The Retinoblastoma protein 449
9.4.4. Other anti-oncogenic transcription factors 456
9.5. Transcription factors and treatment of human disease 461
9.6. Conclusions 471
References 473
CHAPTER 10. CONCLUSIONS AND FUTURE PROSPECTS 485
Index 489
A 489
B 490
C 490
D 492
E 493
F 494
G 495
H 495
I 497
J 498
K 498
L 498
M 499
N 500
O 501
P 501
Q 503
R 503
S 504
T 505
U 506
V 507
W 507
X 507
Y 507
Z 507
Color plates 274