CONTENTS
Preface to the fifth edition
Preface to the first edition
Preface to the second edition
Preface to the third edition
Preface to the fourth edition
Acknowledgements
1 Tissue-specific expression of proteins and messenger RNAs
Summary
1.1 Introduction
1.2 Tissue-specific expression of proteins
Specific methods for studying the protein composition of tissues
General methods for studying the protein composition of tissues
1.3 Tissue-specific expression of messenger RNAs
Specific methods for studying the mRNAs expressed in different tissues
General methods for studying the mRNAs expressed in different tissues
1.4 Conclusions
References
2 The DNA of different cell types is similar in both amount and type
Summary
2.1 Introduction
2.2 DNA loss
DNA loss as a mechanism of gene regulation
Chromosomal studies
Functional studies
Molecular studies
2.3 DNA amplification
DNA amplification as a mechanism of gene regulation
Chromosomal studies
Molecular studies
2.4 DNA rearrangement
2.5 Conclusions
References
3 Gene expression
Summary
3.1 Levels of gene regulation
3.2 Transcription
RNA polymerase I
RNA polymerase III
RNA polymerase II
Common features of transcription by the three RNA polymerases
3.3 Post transcriptional events
Capping
Polyadenylation
RNA splicing
Coupling of transcription and RNA processing within the nucleus
RNA transport
Translation
3.4 Conclusions
References
4 Regulation at transcription
Summary
4.1 Introduction
4.2 Evidence for transcriptional regulation
Evidence from studies of nuclear RNA
Evidence from pulse-labeling studies
Evidence from nuclear run-on assays
Evidence from polytene chromosomes
4.3 Regulation at transcriptional elongation
Initiation of transcription
Transcriptional elongation
4.4 Conclusions
References
5 Post-transcriptional regulation
Summary
5.1 Regulation after transcription?
5.2 Regulation of RNA splicing
RNA splicing
Alternative RNA splicing
Mechanism of alternative RNA splicing
Generality of alternative RNA splicing
5.3 RNA editing
5.4 Regulation of RNA transport
Transport from nucleus to cytoplasm
Transport within the cytoplasm
5.5 Regulation of RNA stability
Cases of regulation by alterations in RNA stability
Mechanisms of stability regulation
Role of stability changes in regulation of gene expression
5.6 Regulation of translation
Cases of translational control
Mechanism of translational control
Significance of translational control
5.7 Inhibition of gene expression by small RNAs
5.8 Conclusions
References
6 Transcriptional control - chromatin structure
Summary
6.1 Introduction
6.2 Commitment to the differentiated state and its stability
6.3 Chromatin structure
6.4 Changes in chromatin structure in active or potentially active genes
Active DNA is organized in a nucleosomal structure
Sensitivity of active chromatin to DNAase I digestion
6.5 Alterations in DNA methylation in active or potentially active genes
Nature of DNA methylation
Evidence that DNA methylation plays a role in regulating chromatin structure
Mechanism by which DNA methylation affects chromatin structure
6.6 Modification of histones in the chromatin of active or potentially active genes
Acetylation
Ubiquitination and sumoylation
Phosphorylation
Methylation
6.7 Changes in chromatin structure in the regulatory regions of active or potentially active genes
DNAase I hypersensitive sites
Chromatin remodeling by proteins capable of displacing nucleosomes or altering their structure
6.8 Other situations in which chromatin structure is regulated
X-chromosome inactivation
Genomic imprinting
6.9 Conclusions
References
7 Transcriptional control - DNA sequence elements
Summary
7.1 Introduction
Relationship of gene regulation in prokaryotes and eukaryotes
Coordinately regulated genes are not linked in eukaryotes
The Britten and Davidson model for the coordinate regulation of unlinked genes
7.2 Short sequence elements located within or adjacent to the gene promoter
Short regulatory elements
The 70[TSP]kDa heat-shock protein gene
Other response elements
DNA binding by short sequence elements
Mechanism of action of promoter regulatory elements
7.3 Enhancers
Regulatory sequences that act at a distance
Tissue-specific activity of enhancers
Mechanism of action of enhancers
7.4 Negatively acting sequence elements
Silencers
Insulators
7.5 Locus control regions
The locus control region
Mechanism of action of LCRs
7.6 Regulation of transcription by RNA polymerases I and III
7.7 Conclusions
References
8 Transcriptional control - transcription factors
Summary
8.1 Introduction
8.2 DNA binding by transcription factors
Introduction
The helix-turn-helix motif
The zinc finger motif
The leucine zipper, the helix-loop-helix motif and the basic DNA binding domain
Other DNA binding domains
8.3 Regulation of transcription
Introduction
Activation domains
How is transcription activated?
Repression of transcription
8.4 What regulates the regulators?
Introduction
Regulated synthesis of transcription factors
Regulated activity of transcription factors
8.5 Conclusions
References
9 Gene regulation and human disease
Summary
9.1 Gene regulation and human disease
Transcriptional regulators
Chromatin remodeling factors
Post-transcriptional events
9.2 Proto-oncogenes
9.3 Elevated expression of oncogenes
9.4 Transcription factors as oncogenes
Fos, Jun and AP1
v-erbA and the thyroid hormone receptor
Other transcription-factor-related oncogenes
9.5 Anti-oncogenes
Nature of anti-oncogenes
p53
The retinoblastoma protein
Other anti-oncogene transcription factors
9.6 Oncogenes/anti-oncogenes: The relationship of cancer and normal cellular function
9.7. Gene regulation and therapy of human diseases
9.8. Conclusions
References
10 Conclusions and future prospects
Index