Genes & Signals

by Ptashne, Mark; Gann, Alexander

• ISBN13: 9780879696337
• ISBN10: 0879696338
• Format: Paperback
• Copyright: 2002-01-01
• Publisher: Cold Spring Harbor Laboratory Pr

Summary

Genes & Signalsanalyzes gene regulation from a new perspective. The first chapter describes mechanisms found in bacteria, and two subsequent chapters discuss which of these is most highly exploited in higher organisms. A final chapter relates these molecular strategies to other enzymatic processes, including those involving kinases, RNA splicing enzymes, proteases, and others. A general theme emerges, one that proposes how a rather restricted set of signals and enzymatic functions has been used in evolution to generate complex life forms of different types.

Table of Contents

Preface	xiii
Foreword	xv
Introduction	1	(10)
Lessons from Bacteria	11	(48)
RNA Polymerase	11	(2)
Regulated Recruitment: The lac Genes	13	(13)
Protein-DNA Interactions	15	(1)
Detecting Physiological Signals	16	(1)
Promoter Recognition and Transcription by RNA Polymerase	17	(1)
Switching the Genes On: Activation by CAP	18	(1)
Cooperative Binding of Proteins to DNA	18	(3)
Cooperative Binding and Gene Activation by CAP	21	(4)
Repression by Lac Repressor	25	(1)
Interim Summary and Extension	25	(1)
More Regulated Recruitment: The Bacteriophageλ	26	(12)
The Switch	28	(1)
Establishing Lysogeny	29	(2)
Analogies with lac	31	(1)
Promoters	32	(1)
Protein-DNA Interactions	32	(1)
Repression	32	(1)
Activation	32	(1)
Detecting Physiological Signals	33	(1)
Making an Efficient Switch	34	(1)
Cooperative Binding of λ Repressor to DNA	34	(3)
Autogenous Control by Repressor	37	(1)
Panel: Antitermination: N and Q	38	(4)
Interim Summary and Extensions	39	(1)
Activation: A Closer Look	39	(2)
DNA binding: A Closer Look	41	(1)
Synergy	41	(1)
Polymerase Activation: glnA and Related Genes	42	(5)
Promoter Recognition by σ54 -containing Polymerase	43	(1)
DNA Binding by NtrC	43	(1)
Detecting the Physiological Signal	43	(1)
Activation by NtrC	43	(2)
Other Activators of σ54 Polymerase	45	(1)
Interim Summary	45	(2)
Panel: Phage T4 Late Genes	47	(1)
Promoter Activation: merT and Related Genes	47	(2)
Promoter Recognition	47	(1)
Detecting the Physiological Signal and Activation	48	(1)
Interim Summary	48	(1)
General Summary	49	(2)
Panel: More on Repression in Bacteria	51	(2)
Footnotes	53	(2)
Bibliography	55	(4)
Yeast: A Single-celled Eukaryote	59	(56)
RNA Polymerase	60	(1)
Other Parts of The Transcriptional Machinery	60	(3)
An Overview of Activation	63	(1)
A Model Case: The Gal Genes	63	(4)
Overview of Regulation of a GAL Gene	64	(1)
Specific DNA Binding	65	(1)
Detecting Physiological Signals	66	(1)
How Gal4 Works	67	(14)
Separate DNA-binding and Activating Regions of Gal4	67	(4)
Activating Region Structure	71	(1)
Independent Mutations Can Increase Activator Strength Additively When Combined	72	(1)
Activating Regions Work with an Efficiency Proportional to Their Lengths	72	(1)
Activating Region---Target Interactions Tolerate Sequence Changes	73	(1)
New Activating Regions Are Easily Generated	73	(2)
Squelching	75	(1)
Recruitment Visualized	76	(1)
Activator Bypass Experiments	76	(2)
Activation by a Heterologous Protein-Protein Interaction	78	(2)
Direct Tethering of the Transcriptional Machinery	80	(1)
Panel: Activator Bypass Experiments	81	(11)
How does Gal4 Recruit Polymerase?	82	(1)
Nucleosomes and Their Modifiers	83	(1)
Targets of Gal4: Experiments Performed In Vitro	84	(1)
Action of Gal4: Experiments Performed In Vivo	85	(1)
What Is Required for Activation?	86	(1)
What Appears at the Gene Upon Activation?	86	(1)
Imposing a Need for Nucleosome Modifiers	87	(1)
Weakening the Gal4-binding Sites or the Gal4-activating region	87	(2)
Cell-cycle Stage-dependent Requirement for Nucleosome Modifiers	89	(1)
Activation: An Interim Summary	89	(2)
Repression by Migl	91	(1)
Signal Integration and Combinatorial Control	92	(3)
Cooperative Binding with Alternative Partners	93	(1)
Sequential Binding of Activators	94	(1)
Silencing	95	(4)
Heterochromatic Chromosomal Regions	95	(3)
Compartmentalization	98	(1)
Panel: Variegation Visualized	99	(1)
Panel: Epigenetics	100	(1)
DNA Looping	101	(2)
Summary	103	(1)
Footnotes	104	(6)
Bibliography	110	(5)
Some Notes on Higher Eukaryotes	115	(28)
Mechanism of Activation: Recruitment	116	(2)
What is Recruited?	118	(4)
Transcriptional Machinery and Promoters	118	(1)
Nucleosomal Templates	119	(1)
Targets	119	(2)
The Human Interferon-β Gene	121	(1)
The Drosophila HSP70 Gene	122	(1)
Repression	122	(1)
Detecting and Transmitting Physiological Signals	123	(2)
Transport Into and Out of the Nucleus	123	(1)
Phosphorylation of Inhibitor or Activator in the Nucleus	124	(1)
Panel: Transport-dependent Proteolysis: The Case of SREBP	125	(1)
Allosteric Change of DNA-bound Activator	126	(1)
Signal Integration, Combinatorial Control, and Alternative Enhancers	126	(3)
The Human Interferon-β Enhancer	126	(2)
The Drosophila eve Gene	128	(1)
Action at a Distance	129	(3)
DNA Methylation, Insulators, and Imprinting	132	(2)
Chromosomal Position and Gene Expression	134	(1)
Compartmentalization	135	(1)
Overview	136	(1)
Footnotes	137	(3)
Bibliography	140	(3)
Enzyme Specificity and Regulation	143	(30)
Ubiquitylation and Proteolysis	144	(2)
Splicing	146	(2)
Imposing Specificity on Kinases	148	(8)
Cyclin-dependent Kinases	149	(1)
Transcriptional Antitermination by TAT	150	(2)
Cytokine Receptors and Signaling through STATs	152	(2)
Growth Factor Receptors	154	(2)
Interim Summary and Extensions	156	(4)
Kinases	157	(1)
Phosphatases	158	(1)
Interpreting Signals	159	(1)
Further Generalizations	160	(7)
Dangers	160	(2)
Interpreting Experiments	162	(1)
Benefits	163	(4)
Footnotes	167	(3)
Bibliography	170	(3)
Afterword	173	(4)
Appendices	177	(10)
Appendix 1: More on Cooperativity	177	(6)
Appendix 2: Topogenic Sequences	183	(2)
Appendix 3: All-or-none Effects and Levels of Gene Expression	185	(2)
Index	187