Latchman. Eukariotic Transciption Factors

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hsp70 gene (cont.)

heat-induced expression, 9–12

promoter, 8, 9, 63

transcriptional elongation, 172

upstream promoter elements, 8, 9,

9–10

hsp90, 250–1, 253

glucocorticoid receptor interaction,

251, 252

Human disease, 293–340

Human immunodeficiency virus (HIV)

DNaseI footprinting assay, 27–8, 29

methylation interference assay, 30–2

promoter, 246

Tat, 172, 173

Hunchback gene, 103, 228, 229

Huntingtin, 296

Huntington’s chorea, 296

Hydroxyl radical footprinting, 28–9

Hydroxyproline, 277

4-Hydroxytamoxifen, 253

Hypertension, 297

Hypoxia inducible factor, see HIF

ICERs (inducible cyclic AMP early

repressors), 234, 235, 236

Id, 124, 187, 188, 219, 286

Id2, 326–7, 327

IFN, see Interferon

IB

acetylation, 273

kinases, 269

in NFB activation, 256, 257, 268–70

phosphorylation, 268–70

protein degradation and processing,

281, 282

Immunoglobulin genes, 1

B cell-specific expression, 245

cancer-inducing translocations, 312,

313

enhancer elements, 14

 gene, 245, 246

promoter elements, 12

Immunoprecipitation, 46, 47–8, 49

In vivo footprinting assay, 32–4

Inducible gene expression, 245, 285

Inhibitory domains, 106, 192–8

Initiation site, transcription, 9

Initiator element, 9

Insulators, 16–17, 202

Insulin resistance, 297

Interferon-, 266

Interferon- (IFN-), 175, 176, 264–5

Interferon-, 266

Interferon-responsive genes, 266

Interleukin-2  receptors, 246

Irx3, 225, 226

Isoleucine, 118

Isomerization, cis-trans, 318

Jun, 299–304, 332

activation domains, 140

as APl component, 299–300

DNA binding, 117, 119, 123, 124

factors stimulating synthesis, 270, 271,

285

glucocorticoid-mediated inhibition,

205

oncogenes targeting, 303

role in cancer, 301–3, 306–7, 308

see also individual oncogenes

P box, 158

p21, 320, 324

p21 inhibitor, 216

p39, 301

p53, 160, 314, 315–22, 332–3

acetylation, 273, 318

competition for CBP/p300, 321

deacetylation, 319

DNA-binding domain, 125

gene deletions, 315, 316

inhibition by MDM2, 189, 190, 192–3,

315, 316, 317, 319, 321

mutations, 315

phosphorylation, 317, 318

Rb-1 regulation, 324–5

p53-related proteins, novel, 321

p62

TCF

, 267

p63, 321

p73, 321

p105, 281, 283

p300, 159–60, 278, 286

methylation, 274, 275

MyoD interaction, 215

p53 acetylation, 273, 319

Paired domain, 101–2, 126

Paired protein (prd), 184

Pancreas, 101

Pax3, 101

mutations, 101, 293

MyoD activation, 101, 217

Pax6, 101, 225, 226

mutations, 293, 293–4, 296

Pax8, alternative splicing, 232–3

Pax factors, 100

Pax proteins, 100–1

DNA binding, 125

PBX proteins, 313

PCAF, steroid receptor interactions, 167

PEA3, 303

Peptidyl prolyl isomerases, 318

Peroxisome proliferator-activated

receptor  (PPAR), 297

Phage 434 repressor, 82

Phenanthroline-copper footprinting,

28–9

Phenylalanine residues, 102, 111

PHO4, 169, 170

PHO5 gene, 169

Phorbol esters, 206, 246

activation of Fos/Jun synthesis, 285,

301

AP1 binding site, 299

NFB activation, 256–7

tumour promotion, 302

Phospholipase C, 262, 263

Phosphorylation, 266–72, 284

acetylation interaction, 274

CBP, 274

CREB, 158–9, 266, 267, 342

CREM, 267

heat-shock factor (HSF), 259, 260, 261,

262, 267

histones, 5

IB, 268–70

MDM2, 317, 318

p53, 317, 318

Rb-1, 270, 323–5

regulating transcription rate, 56

retinoic acid receptor, 65–6

role of TFIIH, 65–6, 68

PHYL, 191

PI(4,5)P

, 262, 263, 269

Pin1, 317–18

Piperidine, 30, 31, 33

Pit-1, 12, 93

CBP interaction, 274

DNA binding, 96–7, 98

mutations, 99, 293, 294, 296

POU domains, 93

Pituitary gland, 12, 97, 99, 293

Pitx2, 220, 328

Platelet-derived growth factor receptor,

312–13

INDEX 355

Polycomb, 200–2, 274

Polymerase chain reaction (PCR), 33, 46

Polyoma, large T oncogene, 331

POMC (pro-opiomelanocortin) gene,

185, 186

PORE sequence, 96, 97

POU domain, 93, 126

POU proteins, 93–100

development of specific cell types, 99

DNA-binding site, 46–7, 125

mutations, 99, 293

novel, 99

regulation of developmental gene

expression, 99

POU-specific domain, 93, 125

POU transcription factors, 41

PPAR (peroxisome proliferator-

activated receptor ), 297

Pro-opiomelanocortin (POMC) gene,

185, 186

Probes, gene cloning, 38–40

Progesterone, 253

Progesterone receptor, 109

Programmed cell death (apoptosis), 315,

321

Prokaryotes, 7

Prolactin gene, 185

Proline hydroxylation, 278, 279

Proline-rich activation domains, 137,

140–1

Prolyl isomerase enzymes, 318

Promoters, gene, 7–9

enhancers and, 13–14

regulatory elements, 9–12

RNA polymerase binding, 62

selective activation, 155

upstream promoter elements, 8, 9,

9–10, 15

Prophet of Pit-1, 99

Protein kinase A, 266, 267

Protein kinase C, 270

Protein kinases, TFIIH activity, 65, 68

Proteins

degradation, 281–3

DNA interactions, methods of study,

23–34

inhibitory, dissociation of, 248, 268

ligand binding, 247–55

modification, 248, 268, 272

post-translational modification, 265–81

processing, 281–3

-protein interactions, 145, 160, 198,

255–65, 268, 341–2

protein-protein interactions, 69–70, 70,

71–2

purification, 34–8

regulation of synthesis, 238

synthesis from cloned genes, 42

Proteolysis, see Degradation, protein

Proto-oncogenes, cellular, 298, 314

PPRI, 109, 110

PRTF, see MCM1

PU-1, 125

Purification, of proteins, 34–8

Quenching phenomenon, 189–90

Raloxifene, 254

Rat, zinc finger proteins, 103

Rb-1, see Retinoblastoma protein

Rb-1 gene, 332

inactivation, 323, 326

Recognition helix, 83–4, 85, 111

bacteriophage proteins, 83, 86

rel oncogene, 312

Repression of transcription, 183–200

by activator degradation, 184, 190–1

direct, 183, 184, 191–200

by forming non-DNA binding complex,

187–9

indirect, 183–91

by masking of DNA binding site, 183–7

mechanisms, 184, 191–2

by quenching activator function,

189–90

Retinoblastoma anti-oncoprotein, 62

Retinoblastoma protein (Rb-1), 314,

322–7, 332

acetylation, 325

E2F interaction, 189, 193, 270

inhibiting effect, 322

phosphorylation, 270, 323–5

repressive activity, 189

targets, 322–6

Retinoblastomas, 322

Retinoic acid, 253

356 INDEX

concentration gradient, 222, 223

Hoxb gene activation, 222–3

as a morphogen, 222

9-cis Retinoic acid, 108, 115

Retinoic acid receptor, 115, 223

DNA binding, 115

ligand binding, 253

phosphorylation, 65–6, 267

Retinoic acid response element, 108, 223

Retinoid X-receptor (RXR), 115–16

Retroviruses, cancer-causing, 297, 312,

331

Rev-T, 312

Ribosomal RNA genes, 55

5S, transcriptional complex, 60–2

regulation by Rb-1, 325

RNA polymerase I transcriptional

complex, 58–60

RLIM co-repressor molecule, 197–8

RNA polymerase I, 55–6, 58–60

Dr1 and, 199

Rb-1 actions, 326

role of TBP, 71, 71–2, 199

stable transcriptional complex, 58–60,

RNA polymerase II, 9, 55–6, 63–7

activator interactions, 147–9

basal transcriptional complex, see Basal

transcriptional complex

C-terminal domain (CTD),

phosphorylation, 65, 151, 172–3

Dr1 and, 199–200

heptapeptide repeat, 56, 147

holoenzyme complex, co-activators,

160

non-TBP/TLF transcription, 72

phosphorylation, 56, 65–6

role of TBP, 68–70, 71–2, 199

stable transcriptional complex, 63–7

ubiquitination, 279

RNA polymerase III, 55–6

Rb-1 actions, 326

role of TBP, 70, 71–2, 199

stable transcriptional complex, 60–2

transcription process, 61–2

transcription units, 60–2

RNA polymerase holoenzyme complex,

66–7

activator actions, 145, 150–1, 162

C-terminal domain, phosphorylation,

204

RNA polymerases, 55–7

DNA-binding site, 62

role of TBP, 71–2

RNA splicing

alternative

CREM, 233–5

thyroid hormone receptor (ErbA),

236

transcription factors, 232–8

polymerase and, 57

Rubinstein–Taybi syndrome, 295–6

Saccharomyces cerevisiae, heat-shock factor

(HSF), 261

SATBI protein, 4–5

Schizosaccharomyces pombe, heat-shock

factor (HSF), 261

Serum response element (SRE), MyoD

action, 216, 217

Serum response factor (SRF), 267

gene cloning, 38

purification, 38

Shh, 225–7

Silencer elements, 16, 198

Simian virus 40, see SV40

SIN3, 202, 203

SINA, 191

Sir2, 319

Skn-l, 119

SLl, 59–60, 70

Snail gene, 103

SNF2 mutations, 294, 296

SnRNA, 93

Somatostatin, 1

Sonic hedgehog (Shh), 225–7

Southern blotting, 42, 91

Sp1, 296

activation domain, 137, 139, 152

AP1 interaction, 17–18

in DNA mobility shift assay, 27

gene cloning, 38, 39

purification, 34–5, 36

repression by Sp3, 184

zinc finger motif, 102–3, 103

Sp1 box, 9

INDEX 357

Sp3, 184, 185, 187

Splicing, alternative, see RNA splicing,

alternative

Splotch mutant, 101

Squelching, 142–3, 149–50, 153

SRC-1

nuclear receptor interactions, 160

steroid receptor interactions, 167

SREBP, 282–3

SRF, see Serum response factor

Stable transcriptional complex, 57–67

characteristics, 57–8

RNA polymerase I, 58–60

RNA polymerase II, 63–7

RNA polymerase III, 60–2

STATs, 266, 274

Steroid hormones, steroid receptor

activation, 166–9

Steroid receptors

activation, 166–9, 253, 254

activation of gene expression, 206–7

DNA binding, 107–9, 113–14, 166

ligand binding, 248–50

see also Glucocorticoid receptor;

Oestrogen receptor

Steroid-thyroid hormone receptor gene

family, see Nuclear receptor gene

superfamily

Stromelysin gene, 303

Sugl, 160

SUMO-1, 279–80, 316, 319

SV40, 325

enhancer, Oct-1 binding, 95

large T oncogenes/oncoprotein, 320,

331, 332

SW15 gene, 103

SWI/SNF complex

chromatin remodelling, 3–4, 7, 164,

170, 171, 176

mutations affecting function, 294, 295,

297

nuclear receptor interactions, 167

RNA polymerase holoenzyme and,

Synthesis of transcription factors,

regulated, 211–29, 286

mechanisms regulating, 229–40

RNA splicing, 232–8

role, 240–1

transcription, 230–2

translation, 238–40

T-cell receptor  gene enhancer, 19

T lymphocytes, 245, 246

activation of gene expression, 246

CD4 expression, 16

LEF-1 factor expression, 18–19

TAFs (TBP-associated factors), 68, 151–7,

161–2

TAF

18, 156

TAF

30, 156

TAF

31 (TAF

40), 138–9, 152, 160,

162

TAF

55, 152

TAF

110, 152

TAF

130 (TAF

105), 156, 296

TAF

145, 155

TAF

250, 154, 161

Tailless gene, 79

TATA-binding protein, see TBP

TATA box, 8–9

activation of transcription and, 155

in RNA polymerase II promoters, 63,

69–70

in RNA polymerase III promoters,

61–2, 70

TBP binding, 68–71, 155

TBP, 67–73

activator interactions, 151–2, 162

binding to non-TATA box promoters,

repressor interactions, 198–9

structure, 69

TATA box binding, 68–71, 155

as universal transcription factor, 67–72

TBP-associated factors, see TAFs

TBP-like factors (TLFs), 72–3

TDF, 103

10T

fibroblast cells, 187, 188, 212–15

TFIIA

activator interactions, 149

inhibitor interactions, 200, 201

in transcriptional complex assembly,

63–4, 66

TFIIB

358 INDEX

activator interactions, 143–5, 148–9,

150, 151, 162

as bridge between TBP and RNA

polymerase II, 69

repressor interactions, 196, 198

in RNA polymerase holoenzyme, 66

in transcriptional complex assembly,

63–4, 66

TFIID

activator interactions, 138–9, 143–5,

148–9, 150

activator targets, 152–3

binding sites, 166–7

chromatin remodelling, 68

multi-protein nature, 68–9, 151

promoter selectivity, 156

TBP component of, 198, 199

in transcriptional complex assembly,

63–4, 66

TFIIE, 65, 66, 68

activator interactions, 151

TFIIE, repressor interactions, 196

TFIIF, 68

activator interactions, 143, 145, 148–9,

151

in RNA polymerase holoenzyme, 66

in transcriptional complex assembly,

64, 65, 66

TFIIH, 68, 71

activator interactions, 145, 149, 151,

162

DNA kinase and helicase activities,

65–6, 68

mutations, 294–5, 296

in RNA polymerase holoenzyme, 66

in transcriptional complex assembly,

65, 66

TFIIJ, 65, 66

TFIIIA, 103

in 5S rRNA gene transcription, 61,

zinc finger motif, 102

TFIIIB, 60–2, 62

Myc interaction, 311

Rb-l interaction, 326

TBP component, 70

TFIIIC, 61, 62, 70

Thymidine kinase, 322

Thymidine kinase gene, 10

Thyroid hormone, 253

binding by v-ErbA, 304–6

Thyroid hormone receptor (ErbA), 285,

304–7

activation of gene expression, 205,

206–7

2 form, 236–7, 306

alternative splicing, 236

cellular vs viral forms, 305–6

DNA binding, 115, 116, 250

inhibition of gene expression, 193–4,

205, 206–7

inhibitory domain, 196–7

ligand-induced regulation, 248–50

mutations, 296–7

repression of transcription, 254

structure, 108, 109

Thyroid response element (TRE), 108,

193, 194

TIF1, 58–60, 62, 160

TIF2, 160

TLFs (TBP-like factors), 72–3

TPA, 299

Transcription, importance of, 1

Transcriptional complexes, see Basal

transcriptional complex; Stable

transcriptional complex

Transfer RNA genes, 55

Translation, regulation of, 238–40

Transretinoic acid, 108, 115

Transthyretin, 231

TRE (thyroid response element), 193,

194

TRF2, 72

Trithorax gene, 164, 202

TTK88, 191

Tubby, 262, 263, 269

Tumour suppressor genes, see anti-

oncogenes

Twist, 264, 265

Two-cysteine two-histidine zinc finger,

102–7

DNA binding, 104–7

transcription factors, 102–4

Tyrosine kinase, 266

U937 monocytic cells, 326

INDEX 359

UBF (upstream binding factor), 325–6

DNA-binding motif, 59–60, 71, 124–5

Ubiquitin, 204, 265, 275, 315–16, 319

Ubiquitination, 275–81

histones, 5, 5–7

Ultrabithorax (Ubx) gene, 79, 80, 81

Ultrabithorax (Ubx) protein, 264

activation domain, 140

gene repression, 192, 193

inducing own expression, 86–7

unc-86, 93, 99

Upstream promoter elements, 8, 9, 9–10,

Valine, 118

VEGF, 106, 107

Ventral neural tube, 225–7

Ventral repression element (VRE), 264,

265

Viruses

DNA, oncogenic, 325, 331