Genes IX

本书目录

Prefacexvi
Genes Are DNA1
Introduction2
DNA Is the Genetic Material of Bacteria3
DNA Is the Genetic Material of Viruses4
DNA Is the Genetic Material of Animal Cells5
Polynucleotide Chains Have Nitrogenous Bases Linked to a Sugar-Phosphate Backbone6
DNA Is a Double Helix6
DNA Replication Is Semiconservative8
DNA Strands Separate at the Replication Fork9
Genetic Information Can Be Provided by DNA or RNA10
Nucleic Acids Hybridize by Base Pairing12
Mutations Change the Sequence of DNA14
Mutations May Affect Single Base Pairs or Longer Sequences15
The Effects of Mutations Can Be Reversed16
Mutations Are Concentrated at Hotspots17
Many Hotspots Result from Modified Bases18
Some Hereditary Agents Are Extremely Small19
Summary20
Genes Code for Proteins23
Introduction24
A Gene Codes for a Single Polypeptide24
Mutations in the Same Gene Cannot Complement25
Mutations May Cause Loss-of-Function or Gain-of-Function26
ALocus May Have Many Different Mutant Alleles27
A Locus May Have More than One Wild-type Allele28
Recombination Occurs by Physical Exchange of DNA28
The Genetic Code Is Triplet30
Every Sequence Has Three Possible Reading Frames31
Prokaryotic Genes Are Colinear with Their Proteins32
Several Processes Are Required to Express the Protein Product of a Gene33
Proteins Are Trans-acting, but Sites on DNA Are Cis-acting35
Summary36
The Interrupted Gene37
Introduction38
An Interrupted Gene Consists of Exons and Introns38
Restriction Endonucleases Are a Key Tool in Mapping DNA39
Organization of Interrupted Genes May Be Conserved40
Exon Sequences Are Conserved but Introns Vary42
Genes Show a Wide Distribution of Sizes43
Some DNA Sequences Code for More Than One Protein45
How Did Interrupted Genes Evolve?47
Some Exons Can Be Equated with Protein Functions49
The Members of a Gene Family Have a Common Organization51
Is All Genetic Information Contained in DNA?53
Summary53
The Content of the Genome55
Introduction56
Genomes Can Be Mapped by Linkage, Restriction Cleavage, or DNA Sequence56
Individual Genomes Show Extensive Variation57
RFLPs and SNPs Can Be Used for Genetic Mapping58
Why Are Genomes So Large?60
Eukaryotic Genomes Contain Both Nonrepetitive and Repetitive DNA Sequences61
Genes Can Be Isolated by the Conservation of Exons63
The Conservation of Genome Organization Helps to Identify Genes65
Organelles Have DNA67
Organelle Genomes Are Circular DNAs That Code for Organelle Proteins69
Mitochondrial DNA Organization Is Variable70
The Chloroplast Genome Codes for Many Proteins and RNAs71
Mitochondria Evolved by Endosymbiosis72
Summary73
Genome Sequences and Gene Numbers76
Introduction77
Bacterial Gene Numbers Range Over an Order of Magnitude77
Total Gene Number Is Known for Several Eukaryotes79
How Many Different Types of Genes Are There?81
The Human Genome Has Fewer Genes Than Expected83
How Are Genes and Other Sequences Distributed in the Genome?85
The Y Chromosome Has Several Male-Specific Genes86
More Complex Species Evolve by Adding New Gene Functions87
How Many Genes Are Essential?89
Genes Are Expressed at Widely Differing Levels92
How Many Genes Are Expressed?93
Expressed Gene Number Can Be Measured En Masse93
Summary94
Clusters and Repeats98
Introduction99
Gene Duplication Is a Major Force in Evolution100
Globin Clusters Are Formed by Duplication and Divergence101
Sequence Divergence Is the Basis for the Evolutionary Clock104
The Rate of Neutral Substitution Can Be Measured from Divergence of Repeated Sequences107
Pseudogenes Are Dead Ends of Evolution108
Unequal Crossing-over Rearranges Gene Clusters109
Genes for rRNA Form Tandem Repeats112
The Repeated Genes for rRNA Maintain Constant Sequence114
Crossover Fixation Could Maintain Identical Repeats115
Satellite DNAs Often Lie in Heterochromatin117
Arthropod Satellites Have Very Short Identical Repeats119
Mammalian Satellites Consist of Hierarchical Repeats120
Minisatellites Are Useful for Genetic Mapping123
Summary125
Messenger RNA127
Introduction128
mRNA Is Produced by Transcription and Is Translated129
Transfer RNA Forms a Cloverleaf130
The Acceptor Stem and Anticodon Are at Ends of the Tertiary Structure131
Messenger RNA Is Translated by Ribosomes132
Many Ribosomes Bind to One mRNA133
The Life Cycle of Bacterial Messenger RNA135
Eukaryotic mRNA Is Modified During or after Its Transcription137
The 5&39; End of Eukaryotic mRNA Is Capped138
The 3&39; Terminus Is Polyadenylated139
Bacterial mRNA Degradation Involves Multiple Enzymes140
mRNA Stability Depends on Its Structure and Sequence141
mRNA Degradation Involves Multiple Activities143
Nonsense Mutations Trigger a Surveillance System144
Eukaryotic RNAs Are Transported145
mRNA Can Be Specifically Localized146
Summary147
Protein Synthesis151
Introduction152
Protein Synthesis Occurs by Initiation, Elongation, and Termination153
Special Mechanisms Control the Accuracy of Protein Synthesis155
Initiation in Bacteria Needs 30S Subunits and Accessory Factors157
A Special Initiator tRNA Starts the Polypeptide Chain158
Use of fMet-tRNA[subscript f] Is Controlled by IF-2 and the Ribosome150
Initiation Involves Base Pairing Between mRNA and rRNA161
Small Subunits Scan for Initiation Sites on Eukaryotic mRNA162
Eukaryotes Use a Complex of Many Initiation Factors164
Elongation Factor Tu Loads Aminoacyl-tRNA into the A Site167
The Polypeptide Chain Is Transferred to Aminoacyl-tRNA168
Translocation Moves the Ribosome169
Elongation Factors Bind Alternately to the Ribosome170
Three Codons Terminate Protein Synthesis172
Termination Codons Are Recognized by Protein Factors173
Ribosomal RNA Pervades Both Ribosomat Subunits175
Ribosomes Have Several Active Centers177
16S rRNA Plays an Active Role in Protein Synthesis179
23S rRNA Has Peptidyl Transferase Activity182
Ribosomal Structures Change When the Subunits Come Together183
Summary183
Using the Genetic Code189
Introduction190
Related Codons Represent Related Amino Acids190
Codon-Anticodon Recognition Involves Wobbling192
tRNAs Are Processed from Longer Precursors194
tRNA Contains Modified Bases194
Modified Bases Affect Anticodon-Codon Pairing196
There Are Sporadic Alterations of the Universal Code197
Novel Amino Acids Can Be Inserted at Certain Stop Codons199
tRNAs Are Charged with Amino Acids by Synthetases200
Aminoacyl-tRNA Synthetases Fall into Two Groups201
Synthetases Use Proofreading to Improve Accuracy203
Suppressor tRNAs Have Mutated Anticodons That Read New Codons206
There Are Nonsense Suppressors for Each Termination Codon207
Suppressors May Compete with Wild-Type Reading of the Code208
The Ribosome Influences the Accuracy of Translation209
Recoding Changes Codon Meanings211
Frameshifting Occurs at Slippery Sequences213
Bypassing Involves Ribosome Movement214
Summary215
Protein Localization218
Introduction220
Passage Across a Membrane Requires a Special Apparatus220
Protein Translocation May Be Posttranslational or Cotranslational221
Chaperones May Be Required for Protein Folding223
Chaperones Are Needed by Newly Synthesized and by Denatured Proteins224
The Hsp70 Family Is Ubiquitous226
Signal Sequences Initiate Translocation227
The Signal Sequence Interacts with the SRP228
The SRP Interacts with the SRP Receptor229
The Translocon Forms a Pore231
Translocation Requires Insertion into the Translocon and Sometimes a Ratchet in the ER233
Reverse Translocation Sends Proteins to the Cytosol for Degradation234
Proteins Reside in Membranes by Means of Hydrophobic Regions235
Anchor Sequences Determine Protein Orientation236
How Do Proteins Insert into Membranes?238
Posttranslational Membrane Insertion Depends on Leader Sequences240
A Hierarchy of Sequences Determines Location within Organelles241
Inner and Outer Mitochondrial Membranes Have Different Translocons243
Peroxisomes Employ Another Type of Translocation System245
Bacteria Use Both Cotranslational and Posttranslational Translocation246
The Sec System Transports Proteins into and Through the Inner Membrane247
Sec-Independent Translocation Systems in E. coli249
Summary250
Transcription256
Introduction258
Transcription Occurs by Base Pairing in a &34;Bubble&34; of Unpaired DNA259
The Transcription Reaction Has Three Stages260
Phage T7 RNA Polymerase Is a Useful Model System251
A Model for Enzyme Movement Is Suggested by the Crystal Structure262
Bacterial RNA Polymerase Consists of Multiple Subunits265
RNA Polymerase Consists of the Core Enzyme and Sigma Factor267
The Association with Sigma Factor Changes at Initiation267
A Stalled RNA Polymerase Can Restart269
How Does RNA Polymerase Find Promoter Sequences?270
Sigma Factor Controls Binding to DNA271
Promoter Recognition Depends on Consensus Sequences272
Promoter Efficiencies Can Be Increased or Decreased by Mutation274
RNA Polymerase Binds to One Face of DNA275
Supercoiling Is an Important Feature of Transcription277
Substitution of Sigma Factors May Control Initiation278
Sigma Factors Directly Contact DNA280
Sigma Factors May Be Organized into Cascades282
Sporulation Is Controlled by Sigma Factors283
Bacterial RNA Polymerase Terminates at Discrete Sites286
There Are Two Types of Terminators in E. coli287
How Does Rho Factor Work?288
Antitermination Is a Regulatory Event291
Antitermination Requires Sites That Are Independent of the Terminators292
Termination and Antitermination Factors Interact with RNA Polymerase293
Summary295
The Operon300
Introduction302
Regulation Can Be Negative or Positive303
Structural Gene Clusters Are Coordinately Controlled304
The lac Genes Are Controlled by a Repressor304
The lac Operon Can Be Induced305
Repressor Is Controlled by a Small-Molecule Inducer306
cis-Acting Constitutive Mutations Identify the Operator308
trans-Acting Mutations Identify the Regulator Gene309
Multimeric Proteins Have Special Genetic Properties309
The Repressor Monomer Has Several Domains310
Repressor Is a Tetramer Made of Two Dimers311
DNA-Binding Is Regulated by an Allosteric Change in Conformation312
Mutant Phenotypes Correlate with the Domain Structure312
Repressor Protein Binds to the Operator313
Binding of Inducer Releases Repressor from the Operator314
Repressor Binds to Three Operators and Interacts with RNA Polymerase315
Repressor Is Always Bound to DNA316
The Operator Competes with Low-Affinity Sites to Bind Repressor317
Repression Can Occur at Multiple Loci319
Cyclic AMP Is an Effector That Activates CRP to Act at Many Operons320
CRP Functions in Different Ways in Different Target Operons321
Translation Can Be Regulated323
r-Protein Synthesis Is Controlled by Autogenous Regulation325
Phage T4 p32 Is Controlled by an Autogenous Circuit326
Autogenous Regulation Is Often Used to Control Synthesis of Macromolecular Assemblies327
Summary328
Regulatory RNA331
Introduction332
Alternative Secondary Structures Control Attenuation333
Termination of Bacillus subtilis trp Genes Is Controlled by Tryptophan and by tRNA[superscript Trp]333
The Escherichia coli tryptophan Operon Is Controlled by Attenuation335
Attenuation Can Be Controlled by Translation336
Antisense RNA Can Be Used to Inactivate Gene Expression338
Small RNA Molecules Can Regulate Translation339
Bacteria Contain Regulator RNAs341
MicroRNAs Are Regulators in Many Eukaryotes342
RNA Interference Is Related to Gene Silencing343
Summary345
Phage Strategies349
Introduction350
Lytic Development Is Divided into Two Periods352
Lytic Development Is Controlled by a Cascade353
Two Types of Regulatory Event Control the Lytic Cascade354
The T7 and T4 Genomes Show Functional Clustering355
Lambda Immediate Early and Delayed Early Genes Are Needed for Both Lysogeny and the Lytic Cycle356
The Lytic Cycle Depends on Antitermination357
Lysogeny Is Maintained by Repressor Protein359
The Repressor and Its Operators Define the Immunity Region360
The DNA-Binding Form of Repressor Is a Dimer361
Repressor Uses a Helix-Turn-Helix Motif to Bind DNA362
The Recognition Helix Determines Specificity for DNA363
Repressor Dimers Bind Cooperatively to the Operator364
Repressor at 0[subscript R]2 Interacts with RNA Polymerase at P[subscript RM]365
Repressor Maintains an Autogenous Circuit366
Cooperative Interactions Increase the Sensitivity of Regulation367
The cII and cIII Genes Are Needed to Establish Lysogeny368
A Poor Promoter Requires cII Protein369
Lysogeny Requires Several Events369
The cro Repressor Is Needed for Lytic Infection371
What Determines the Balance Between Lysogeny and the Lytic Cycle?373
Summary374
The Replicon376
Introduction377
Replicons Can Be Linear or Circular378
Origins Can Be Mapped by Autoradiography and Electrophoresis379
Does Methylation at the Origin Regulate Initiation?380
Origins May Be Sequestered after Replication381
Each Eukaryotic Chromosome Contains Many Replicons383
Replication Origins Can Be Isolated in Yeast384
Licensing Factor Controls Eukaryotic Rereplication385
Licensing Factor Consists of MCM Proteins386
D Loops Maintain Mitochondrial Origins388
Summary389
Extrachromosomal Replicons392
Introduction393
The Ends of Linear DNA Are a Problem for Replication393
Terminal Proteins Enable Initiation at the Ends of Viral DNAs394
Rolling Circles Produce Multimers of a Replicon396
Rolling Circles Are Used to Replicate Phage Genomes397
The F Plasmid Is Transferred by Conjugation between Bacteria398
Conjugation Transfers Single-Stranded DNA400
The Bacterial Ti Plasmid Causes Crown Gall Disease in Plants401
T-DNA Carries Genes Required for Infection402
Transfer of T-DNA Resembles Bacterial Conjugation405
Summary407
Bacterial Replication Is Connected to the Cell Cycle408
Introduction409
Replication Is Connected to the Cell Cycle410
The Septum Divides a Bacterium into Progeny That Each Contain a Chromosome411
Mutations in Division or Segregation Affect Cell Shape412
FtsZ Is Necessary for Septum Formation413
min Genes Regulate the Location of the Septum415
Chromosomal Segregation May Require Site-Specific Recombination415
Partitioning Involves Separation of the Chromosomes417
Single-Copy Plasmids Have a Partitioning System419
Plasmid Incompatibility Is Determined by the Replicon421
The ColE1 Compatibility System Is Controlled by an RNA Regulator422
How Do Mitochondria Replicate and Segregate?424
Summary425
DNA Replication428
Introduction429
DNA Polymerases Are the Enzymes That Make DNA430
DNA Polymerases Have Various Nuclease Activities431
DNA Polymerases Control the Fidelity of Replication432
DNA Polymerases Have a Common Structure433
DNA Synthesis Is Semidiscontinuous434
The [phi]X Model System Shows How Single-Stranded DNA Is Generated for Replication435
Priming Is Required to Start DNA Synthesis437
DNA Polymerase Holoenzyme Has Three Subcomplexes439
The Clamp Controls Association of Core Enzyme with DNA440
Coordinating Synthesis of the Lagging and Leading Strands442
Okazaki Fragments Are Linked by Ligase443
Separate Eukaryotic DNA Polymerases Undertake Initiation and Elongation444
Phage T4 Provides Its Own Replication Apparatus445
Creating the Replication Forks at an Origin448
Common Events in Priming Replication at the Origin450
The Primosome Is Needed to Restart Replication451
Summary453
Homologous and Site-Specific Recombination457
Introduction459
Homologous Recombination Occurs between Synapsed Chromosomes460
Breakage and Reunion Involves Heteroduplex DNA462
Double-Strand Breaks Initiate Recombination464
Recombining Chromosomes Are Connected by the Synaptonemal Complex465
The Synaptonemal Complex Forms after Double-Strand Breaks467
Pairing and Synaptonemal Complex Formation Are Independent469
The Bacterial RecBCD System Is stimulated by chi Sequences470
Strand-Transfer Proteins Catalyze Single-Strand Assimilation471
The Ruv System Resolves Holliday Junctions473
Gene Conversion Accounts for Interallelic Recombination475
Supercoiling Affects the Structure of DNA476
Topoisomerases Relax or Introduce Supercoils in DNA478
Topoisomerases Break and Reseal Strands480
Gyrase Functions by Coil Inversion481
Specialized Recombination Involves Specific Sites482
Site-Specific Recombination Involves Breakage and Reunion484
Site-Specific Recombination Resembles Topoisomerase Activity484
Lambda Recombination Occurs in an Intasome486
Yeast Can Switch Silent and Active Loci for Mating Type488
The MAT Locus Codes for Regulator Proteins490
Silent Cassettes at HML and HMR Are Repressed492
Unidirectional Transposition Is Initiated by the Recipient MAT Locus493
Regulation of HO Expression Controls Switching494
Summary496
Repair Systems499
Introduction500
Repair Systems Correct Damage to DNA502
Excision Repair Systems in E. coli503
Excision-Repair Pathways in Mammalian Cells504
Base Flipping Is Used by Methylases and Glycosylases506
Error-Prone Repair and Mutator Phenotypes507
Controlling the Direction of Mismatch Repair507
Recombination-Repair Systems in E. coli510
Recombination Is an Important Mechanism to Recover from Replication Errors511
RecA Triggers the SOS System513
Eukaryotic Cells Have Conserved Repair Systems515
A Common System Repairs Double-Strand Breaks516
Summary518
Transposons521
Introduction522
Insertion Sequences Are Simple Transposition Modules524
Composite Transposons Have IS Modules525
Transposition Occurs by Both Replicative and Nonreplicative Mechanisms527
Transposons Cause Rearrangement of DNA528
Common Intermediates for Transposition530
Replicative Transposition Proceeds through a Cointegrate531
Nonreplicative Transposition Proceeds by Breakage and Reunion533
TnA Transposition Requires Transposase and Resolvase534
Transposition of Tn10 Has Multiple Controls536
Controlling Elements in Maize Cause Breakage and Rearrangements538
Controlling Elements Form Families of Transposons540
Spm Elements Influence Gene Expression542
The Role of Transposable Elements in Hybrid Dysgenesis544
P Elements Are Activated in the Germline545
Summary546
Retroviruses and Retroposons550
Introduction551
The Retrovirus Life Cycle Involves Transposition-Like Events551
Retroviral Genes Code for Polyproteins552
Viral DNA Is Generated by Reverse Transcription554
Viral DNA Integrates into the Chromosome556
Retroviruses May Transduce Cellular Sequences558
Yeast Ty Elements Resemble Retroviruses559
Many Transposable Elements Reside in Drosophila melanogaster561
Retroposons Fall into Three Classes562
The Alu Family Has Many Widely Dispersed Members564
Processed Pseudogenes Originated as Substrates for Transposition565
LINES Use an Endonuclease to Generate a Priming End566
Summary567
Immune Diversity570
Introduction572
Clonal Selection Amplifies Lymphocytes That Respond to Individual Antigens574
Immunoglobulin Genes Are Assembled from Their Parts in Lymphocytes575
Light Chains Are Assembled by a Single Recombination577
Heavy Chains Are Assembled by Two Recombinations579
Recombination Generates Extensive Diversity580
Immune Recombination Uses Two Types of Consensus Sequence581
Recombination Generates Deletions or Inversions582
Allelic Exclusion Is Triggered by Productive Rearrangement582
The RAG Proteins Catalyze Breakage and Reunion584
Early Heavy Chain Expression Can Be Changed by RNA Processing586
Class Switching Is Caused by DNA Recombination587
Switching Occurs by a Novel Recombination Reaction589
Somatic Mutation Generates Additional Diversity in Mouse and Human Being590
Somatic Mutation Is Induced by Cytidine Deaminase and Uracil Glycosylase591
Avian Immunoglobulins Are Assembled from Pseudogenes593
B Cell Memory Allows a Rapid Secondary Response594
T Cell Receptors Are Related to Immunoglobulins595
The T Cell Receptor Functions in Conjunction with the MHC597
The Major Histocompatibility Locus Codes for Many Genes of the Immune System599
Innate Immunity Utilizes Conserved Signaling Pathways602
Summary604
Promoters and Enhancers609
Introduction610
Eukaryotic RNA Polymerases Consist of Many Subunits612
Promoter Elements Are Defined by Mutations and Footprinting613
RNA Polymerase I Has a Bipartite Promoter614
RNA Polymerase III Uses Both Downstream and Upstream Promoters615
TF[subscript III]B Is the Commitment Factor for Pol III Promoters616
The Startpoint for RNA Polymerase II618
TBP Is a Universal Factor619
TBP Binds DNA in an Unusual Way620
The Basal Apparatus Assembles at the Promoter621
Initiation Is Followed by Promoter Clearance623
A Connection between Transcription and Repair625
Short Sequence Elements Bind Activators627
Promoter Construction Is Flexible but Context Can Be Important628
Enhancers Contain Bidirectional Elements That Assist Initiation629
Enhancers Contain the Same Elements That Are Found at Promoters630
Enhancers Work by Increasing the Concentration of Activators Near the Promoter631
Gene Expression Is Associated with Demethylation632
CpG Islands Are Regulatory Targets634
Summary635
Activating Transcription640
Introduction641
There Are Several Types of Transcription Factors642
Independent Domains Bind DNA and Activate Transcription643
The Two Hybrid Assay Detects Protein-Protein Interactions645
Activators Interact with the Basal Apparatus646
Some Promoter-Binding Proteins Are Repressors648
Response Elements Are Recognized by Activators649
There Are Many Types of DNA-Binding Domains651
A Zinc Finger Motif Is a DNA-Binding Domain652
Steroid Receptors Are Activators653
Steroid Receptors Have Zinc Fingers655
Binding to the Response Element Is Activated by Ligand-Binding656
Steroid Receptors Recognize Response Elements by a Combinatorial Code657
Homeodomains Bind Related Targets in DNA658
Helix-Loop-Helix Proteins Interact by Combinatorial Association660
Leucine Zippers Are Involved in Dimer Formation662
Summary663
RNA Splicing and Processing667
Introduction669
Nuclear Splice Junctions Are Short Sequences670
Splice Junctions Are Read in Pairs671
Pre-mRNA Splicing Proceeds through a Lariat673
snRNAs Are Required for Splicing674
U1 snRNP Initiates Splicing676
The E Complex Can Be Formed by Intron Definition or Exon Definition678
5 snRNPs Form the Spliceosome679
An Alternative Splicing Apparatus Uses Different snRNPs681
Splicing Is Connected to Export of mRNA682
Group II Introns Autosplice via Lariat Formation683
Alternative Splicing Involves Differential Use of Splice Junctions685
trans-Splicing Reactions Use Small RNAs688
Yeast tRNA Splicing Involves Cutting and Rejoining690
The Splicing Endonuclease Recognizes tRNA691
tRNA Cleavage and Ligation Are Separate Reactions692
The Unfolded Protein Response Is Related to tRNA Splicing693
The 3&39; Ends of polI and polIII Transcripts Are Generated by Termination694
The 3&39; Ends of mRNAs Are Generated by Cleavage and Polyadenylation695
Cleavage of the 3&39; End of Histone mRNA May Require a Small RNA697
Production of rRNA Requires Cleavage Events697
Small RNAs Are Required for rRNA Processing699
Summary700
Catalytic RNA706
Introduction707
Group I Introns Undertake Self-Splicing by Transesterification707
Group I Introns Form a Characteristic Secondary Structure709
Ribozymes Have Various Catalytic Activities711
Some Group I Introns Code for Endonucleases That Sponsor Mobility715
Group II Introns May Code for Multifunction Proteins716
Some Autosplicing Introns Require Maturases717
The Catalytic Activity of RNAase P Is Due to RNA718
Viroids Have Catalytic Activity718
RNA Editing Occurs at Individual Bases720
RNA Editing Can Be Directed by Guide RNAs721
Protein Splicing Is Autocatalytic724
Summary725
Chromosomes729
Introduction730
Viral Genomes Are Packaged into Their Coats731
The Bacterial Genome Is a Nucleoid734
The Bacterial Genome Is Supercoiled735
Eukaryotic DNA Has Loops and Domains Attached to a Scaffold736
Specific Sequences Attach DNA to an Interphase Matrix737
Chromatin Is Divided into Euchromatin and Heterochromatin738
Chromosomes Have Banding Patterns740
Lampbrush Chromosomes Are Extended741
Polytene Chromosomes Form Bands742
Polytene Chromosomes Expand at Sites of Gene Expression743
The Eukaryotic Chromosome Is a Segregation Device744
Centromeres May Contain Repetitive DNA746
Centromeres Have Short DNA Sequences in S. cerevisiae747
The Centromere Binds a Protein Complex748
Telomeres Have Simple Repeating Sequences748
Telomeres Seat the Chromosome Ends749
Telomeres Are Synthesized by a Ribonucleoprotein Enzyme750
Telomeres Are Essential for Survival752
Summary753
Nucleosomes757
Introduction758
The Nucleosome Is the Subunit of All Chromatin759
DNA Is Coiled in Arrays of Nucleosomes761
Nucleosomes Have a Common Structure762
DNA Structure Varies on the Nucleosomal Surface763
The Periodicity of DNA Changes on the Nucleosome766
Organization of the Histone Octamer767
The Path of Nucleosomes in the Chromatin Fiber769
Reproduction of Chromatin Requires Assembly of Nucleosomes771
Do Nucleosomes Lie at Specific Positions?774
Are Transcribed Genes Organized in Nucleosomes?777
Histone Octamers Are Displaced by Transcription779
Nucleosome Displacement and Reassembly Require Special Factors781
Insulators Block the Actions of Enhancers and Heterochromatin781
Insulators Can Define a Domain783
Insulators May Act in One Direction784
Insulators Can Vary in Strength785
DNAase Hypersensitive Sites Reflect Changes in Chromatin Structure786
Domains Define Regions That Contain Active Genes788
An LCR May Control a Domain789
What Constitutes a Regulatory Domain?790
Summary791
Controlling Chromatin Structure796
Introduction797
Chromatin Can Have Alternative States797
Chromatin Remodeling Is an Active Process798
Nucleosome Organization May Be Changed at the Promoter801
Histone Modification Is a Key Event802
Histone Acetylation Occurs in Two Circumstances805
Acetylases Are Associated with Activators806
Deacetylases Are Associated with Repressors808
Methylation of Histones and DNA Is Connected808
Chromatin States Are Interconverted by Modification809
Promoter Activation Involves an Ordered Series of Events809
Histone Phosphorylation Affects Chromatin Structure810
Some Common Motifs Are Found in Proteins That Modify Chromatin811
Summary812
Epigenetic Effects Are Inherited818
Introduction819
Heterochromatin Propagates from a Nucleation Event820
Heterochromatin Depends on Interactions with Histones822
Polycomb and Trithorax Are Antagonistic Repressors and Activators824
X Chromosomes Undergo Global Changes826
Chromosome Condensation Is Caused by Condensins828
DNA Methylation Is Perpetuated by a Maintenance Methylase830
DNA Methylation Is Responsible for Imprinting832
Oppositely Imprinted Genes Can Be Controlled by a Single Center834
Epigenetic Effects Can Be Inherited835
Yeast Prions Show Unusual Inheritance836
Prions Cause Diseases in Mammals839
Summary840
Glossary845
Index867
· · · · · ·