Transcription Factors

Book Cover......Page 1
Half-Title......Page 2
Title......Page 4
Copyright......Page 5
Contents......Page 6
Contributors......Page 14
Abbreviations......Page 16
Preface......Page 21
1. Introduction: promoter function and strategies in gene control......Page 23
3. Rate-limiting steps in gene expression......Page 24
4. Assembly and regulation of the TATA-binding protein and associated factors......Page 25
5. Recruitment of the RNA polymerase II holoenzyme......Page 28
5.1 Transcription factor TFIIB......Page 29
5.3 The CTD and the SRB/Mediator complex......Page 30
5.4 Transcription factors TFIIE and TFIIH......Page 31
7. Conclusions and prospects......Page 32
References......Page 33
1. Introduction......Page 38
2.2 DNA-binding domains......Page 39
2.3 Activation domains......Page 40
2.4 General transcription factors as activation domain targets......Page 43
2.5 Coactivators as activation domain targets......Page 44
3. Organization of cis-acting regulatory regions and combinatorial control......Page 45
3.1 Combinatorial interactions and developmental complexity......Page 46
3.2 Combinatorial interactions and signal transduction......Page 47
3.3 Enhanceosomes and the mechanism of transcriptional synergy......Page 48
References......Page 51
1. Introduction......Page 55
2.1 The radial loop and helical-folding models of chromosome structure......Page 56
2.2 The nuclear matrix, scaffold and skeleton: protein components and their function......Page 57
2.3 Chromosome domains, position effect and locus control regions......Page 59
3.1 Features......Page 60
3.2 Histone H1 and higher-order chromatin structure......Page 62
4.2 Structural and functional consequences of acetylation of the core histones......Page 63
4.3 Structural and functional consequences of phosphorylation and ubiquitination of the core histones......Page 65
5.1 The SAGA (PCAF) activator complex......Page 66
5.2 Histone acetyltransferases p300 and TAFII250......Page 67
5.3 The SWI/SNF complex......Page 68
6.1 Histone deacetylase and mammalian Sin3......Page 69
6.2 Nuclear hormone receptors and histone deacetylase......Page 70
6.3 DNA methylation and transcriptional control......Page 71
References......Page 74
1. Principles of protein—DNA recognition......Page 84
1.1 Shape recognition......Page 85
1.3 Role of water......Page 86
1.4 Role of DNA structure......Page 87
1.6 Multiple recognition sites......Page 88
2.1 Helix-turn-helix containing DNA-binding domains......Page 89
2.2 Zinc-containing DNA-binding domains......Page 92
2.3 Other DNA-binding domains that use a-helices to bind DNA......Page 94
2.4 DNA-binding domains that use b-strands to bind DNA......Page 96
2.5  b-barrels and b-sandwiches......Page 97
References......Page 98
1. Introduction......Page 104
2.1 Transcription factors governing yeast cell-cycle progression......Page 105
3. Cdk7 and Cdk8: two components of the basal transcription machinery......Page 107
4. The pRB family of proteins......Page 108
4.2 Mechanisms of retinoblastoma protein......Page 111
5.1 E2F family members......Page 113
5.2 E2F as a transcriptional activator and repressor......Page 115
6. c-Myc transcription factor and its partners......Page 116
7. Role of p53 as transcription factor and growth suppressor......Page 117
8.1 Phosphorylation of basal transcription factors......Page 119
8.2 Cell-cycle-dependent changes in chromatin......Page 120
8.3 Post-initiation regulatory mechanisms......Page 121
References......Page 122
1. Introduction......Page 131
2.1 Type I: protein kinase cascades to transcription factor substrates......Page 132
2.2 Type II: protein kinase cascades to coactivator and corepressor proteins......Page 134
2.4 Type IV: signaling by small molecules......Page 135
3.1 Linear, convergent and divergent signaling......Page 136
3.2 Specificity-determining mechanisms......Page 138
4. Modification of transcription factor activity......Page 140
4.1 Regulation of nuclear translocation......Page 142
4.2 Regulation of intrinsic transcription factor activity......Page 144
4.3 Interaction with coregulatory proteins......Page 146
5.1 Genome sequencing......Page 147
5.4 Signaling by acetylation......Page 148
References......Page 149
1. Introduction......Page 153
2.1 B-cell development......Page 154
2.2 Basic helix-loop-helix proteins encoded by the E2A gene......Page 155
2.3 Early B cell factor (EBF)......Page 158
2.4 Pax-5/B cell-specific activator protein (BSAP)......Page 161
3.1 T cell development......Page 164
3.3 Control modules of the CD4 gene......Page 166
3.4 Transcription factors that control CD4 expression and T-cell development......Page 169
4. Conclusions......Page 172
References......Page 173
1. Introduction......Page 181
2. The family and its ligands......Page 182
3.1 Target gene recognition......Page 186
3.2 Genetics of nuclear receptors......Page 188
4.2 The DNA-binding domain encompasses region C......Page 190
4.3 Region D, a hinge with compartmentalization functions......Page 191
4.4 Region E encompasses the ligand-binding domain and activation function 2 (AF-2)......Page 192
5.1 Chromatin modifying nuclear receptor coregulators......Page 195
5.3 Recruitment of the RNA polymerase II holoenzyme—the second step of coactivation......Page 207
5.4 Interaction of nuclear receptors with components of the basal transcription machinery......Page 208
6.1 AP1 nuclear receptor crosstalk......Page 210
6.2 NF-kB and nuclear receptor crosstalk......Page 211
7. Deregulation in disease and novel therapeutic targets......Page 212
7.1 Novel perspectives for therapy......Page 213
8. Conclusions......Page 214
References......Page 216
1. Introduction......Page 228
2. Summary of early embryonic development of the mammalian body plan......Page 231
3. Hox protein function: regulation of transcription......Page 232
4. Homeodomain cofactors: TALE proteins......Page 233
5. Other HOX and PBC cofactors: PREP, Hth and Meis......Page 235
6. Subcellular localization......Page 236
7. ‘Coselective binding’ model for Hox functional specificity versus the ‘widespread binding/activity regulation’ model......Page 237
8. Transcriptional regulation of Hox gene expression in the developing embryo......Page 238
8.1 Hoxa1 and Hoxa2......Page 240
8.2 Hoxa4......Page 241
8.3 Hoxb1......Page 242
References......Page 243
1. Introduction......Page 248
2.1 Hepatocyte gene-regulatory modules......Page 249
2.2  Hepatocyte nuclear factors HNF3 and HNF6......Page 253
2.3 C/EBP and DBP-related factors......Page 255
2.4 HNF1......Page 257
2.5 HNF4 and DR1-binding nuclear receptors......Page 258
2.6 Regulators of additional inducible transcriptional responses in hepatocytes......Page 260
3. Developmental relationship to pancreas and intestine......Page 261
4. Future directions......Page 263
References......Page 264
1. Introduction......Page 274
2.1 TFs in early neural induction......Page 275
2.2 Role of endoderm in neural induction......Page 277
2.3 Role of mesoderm in neural induction......Page 278
3.1 Forebrain patterning......Page 279
3.2 Role of TFs in dorsal/ventral telencephalon formation......Page 280
3.4 Role of TFs in hindbrain development......Page 283
4.2 Ventral signals, A/P axis and TFs......Page 285
4.3 Dorsal signals and TFs......Page 286
5.1 Mutations in TFs that lead to nervous system defects......Page 287
5.2 TFs regulate neuronal survival during injury and disease......Page 290
6. Conclusions......Page 292
References......Page 294
1. Introduction......Page 305
2. Chimeric transcription factors in human leukemias......Page 306
2.1 ALL and E2A protein chimeras: All may not be as it seems......Page 307
2.2 Histone deacetylases and chimeric oncoproteins: a newly recognized recurring theme......Page 312
3. Chimeric transcription factors in human sarcomas......Page 319
3.1 A diverse variety of sarcomas contain translocations that target EWS......Page 320
References......Page 323
Index......Page 333