Genes and Signals

Contents......Page 8
Preface......Page 14
Foreword......Page 16
Introduction......Page 18
RNA POLYMERASE......Page 28
REGULATED RECRUITMENT: THE lac GENES......Page 30
Protein-DNA Interactions......Page 32
Detecting Physiological Signals......Page 33
Promoter Recognition and Transcription by RNA Polymerase......Page 34
Cooperative Binding of Proteins to DNA......Page 35
Cooperative Binding and Gene Activation by CAP......Page 38
Interim Summary and Extension......Page 42
MORE REGULATED RECRUITMENT: THE BACTERIOPHAGE λ......Page 43
The Switch......Page 45
Establishing Lysogeny......Page 46
Analogies with lac......Page 48
Activation......Page 49
Detecting Physiological Signals......Page 50
Cooperative Binding of λ Repressor to DNA......Page 51
Autogenous Control by Repressor......Page 54
PANEL: Antitermination: N and Q......Page 55
Activation: A Closer Look......Page 56
Synergy......Page 58
POLYMERASE ACTIVATION: glnA AND RELATED GENES......Page 59
Activation by NtrC......Page 60
Interim Summary......Page 62
Promoter Recognition......Page 64
Interim Summary......Page 65
GENERAL SUMMARY......Page 66
PANEL: More on Repression in Bacteria......Page 68
FOOTNOTES......Page 70
BIBLIOGRAPHY......Page 72
CHAPTER 2  Yeast: A Single-celled Eukaryote......Page 76
OTHER PARTS OF THE TRANSCRIPTIONAL MACHINERY......Page 77
A MODEL CASE: THE GAL GENES......Page 80
Overview of Regulation of a GAL Gene......Page 81
Specific DNA Binding......Page 82
Detecting Physiological Signals......Page 83
Separate DNA-binding and Activating Regions of Gal4......Page 84
Activating Region Structure......Page 88
Activating Regions Work with an Efficiency Proportional to Their Lengths......Page 89
New Activating Regions Are Easily Generated......Page 90
Squelching......Page 92
Activator Bypass Experiments......Page 93
Activation by a Heterologous Protein-Protein Interaction......Page 95
Direct Tethering of the Transcriptional Machinery......Page 97
PANEL: Activator Bypass Experiments......Page 98
How does Gal4 Recruit Polymerase?......Page 99
Nucleosomes and Their Modifiers......Page 100
Targets of Gal4: Experiments Performed In Vitro......Page 101
Action of Gal4: Experiments Performed In Vivo......Page 102
What Appears at the Gene Upon Activation?......Page 103
Weakening the Gal4-binding Sites or the Gal4-activating region......Page 104
Activation: An Interim Summary......Page 106
Repression by Mig1......Page 108
SIGNAL INTEGRATION AND COMBINATORIAL CONTROL......Page 109
Cooperative Binding with Alternative Partners......Page 110
Sequential Binding of Activators......Page 111
Heterochromatic Chromosomal Regions......Page 112
Compartmentalization......Page 115
PANEL: Variegation Visualized......Page 116
PANEL: Epigenetics......Page 117
DNA LOOPING......Page 118
SUMMARY......Page 120
FOOTNOTES......Page 121
BIBLIOGRAPHY......Page 127
CHAPTER 3  Some Notes on Higher Eukaryotes......Page 132
MECHANISM OF ACTIVATION: RECRUITMENT......Page 133
Transcriptional Machinery and Promoters......Page 135
Targets......Page 136
The Human Interferon-β Gene......Page 138
REPRESSION......Page 139
Transport Into and Out of the Nucleus......Page 140
Phosphorylation of Inhibitor or Activator in the Nucleus......Page 141
PANEL: Transport-dependent Proteolysis: The Case of SREBP......Page 142
The Human Interferon-β Enhancer......Page 143
The Drosophila eve Gene......Page 145
ACTION AT A DISTANCE......Page 146
DNA METHYLATION, INSULATORS, AND IMPRINTING......Page 149
CHROMOSOMAL POSITION AND GENE EXPRESSION......Page 151
COMPARTMENTALIZATION......Page 152
OVERVIEW......Page 153
FOOTNOTES......Page 154
BIBLIOGRAPHY......Page 157
CHAPTER 4  Enzyme Specificity and Regulation......Page 160
UBIQUITYLATION AND PROTEOLYSIS......Page 161
SPLICING......Page 163
IMPOSING SPECIFICITY ON KINASES......Page 165
Cyclin-dependent Kinases......Page 166
Transcriptional Antitermination by TAT......Page 167
Cytokine Receptors and Signaling through STATs......Page 169
Growth Factor Receptors......Page 171
INTERIM SUMMARY AND EXTENSIONS......Page 173
Kinases......Page 174
Phosphatases......Page 175
Interpreting Signals......Page 176
Dangers......Page 177
Interpreting Experiments......Page 179
Benefits......Page 180
FOOTNOTES......Page 184
BIBLIOGRAPHY......Page 187
Afterword......Page 190
Appendix 1: More on Cooperativity......Page 194
Appendix 2: Topogenic Sequences......Page 200
Appendix 3: All-or-none Effects and Levels of Gene Expression......Page 202
C......Page 204
G......Page 205
K......Page 206
N......Page 207
S......Page 208
Y......Page 209