Details

Genome Organization And Function In The Cell Nucleus


Genome Organization And Function In The Cell Nucleus


1. Aufl.

von: Karsten Rippe

155,00 €

Verlag: Wiley-VCH
Format: EPUB
Veröffentl.: 09.01.2012
ISBN/EAN: 9783527640003
Sprache: englisch
Anzahl Seiten: 594

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Beschreibungen

By way of its clear and logical structure, as well as abundant highresolution illustrations, this is a systematic survey of the players and pathways that control genome function in the mammalian cell nucleus. As such, this handbook and reference ties together recently gained knowledge from a variety of scientific disciplines and approaches, dissecting all major genomic events: transcription, replication, repair, recombination and chromosome segregation. A special emphasis is put on transcriptional control, including genome-wide interactions and non-coding RNAs, chromatin structure, epigenetics and nuclear organization. With its focus on fundamental mechanisms and the associated biomolecules, this will remain essential reading for years to come.
Preface xix List of Contributors xxi 1 Deciphering DNA Sequence Information 1 Mark Kaganovich and Michael Snyder 1.1 Introduction 1 1.2 Genes and Transcribed Regions 1 1.3 Non-Coding Genomic Elements 4 1.4 Regulatory Information 10 1.5 Individual Genetic Polymorphisms and Their Effect on Gene Expression 16 1.6 Conclusion 16 2 DNA Methylation 21 Carina Frauer, Fabio Spada, and Heinrich Leonhardt 2.1 Introduction 21 2.2 Eukaryotic DNA Methyltransferases 24 2.3 Distribution of 5-Methylcytosine in the Mammalian Genome 27 2.4 Control of Gene Expression by DNA Methylation 31 2.5 DNA Demethylation 37 3 Nucleosomes as Control Elements for Accessing the Genome 55 Mekonnen Lemma Dechassa and Karolin Luger 3.1 Introduction and Basic Terminology 55 3.2 Nucleosomes are the Building Blocks of Chromatin 56 3.3 Nucleosomes Are Dynamic Macromolecular Assemblies 63 3.4 Histone Variants and Their Effect on Nucleosome Structure and Dynamics 66 3.5 Histone Modifications in Nucleosome and Chromatin Structure 68 3.6 DNA Sequence and Nucleosome Positioning 70 3.7 Histone Chaperones and Chromatin Dynamics 73 3.8 Outlook and Concluding Remarks 75 4 Histone Modifications and Their Role as Epigenetic Marks 89 Karl Nightingale 4.1 The Complexity of Histone Modifications 89 4.2 Regulating Histone Modifications in Chromatin 93 4.3 The “Histone Code” Hypothesis 95 4.4 Exploiting the Complexity of the Histone Code: “Crosstalk” Between Different Modifications 98 4.5 Are Histone Modifications Heritable Epigenetic Marks? 104 4.6 Conclusions 106 5 Chromatin Remodeling and Nucleosome Positioning 111 Gernot La¨ngst, Vladimir B. Teif, and Karsten Rippe 5.1 Introduction 111 5.2 Chromatin Remodeling Complexes 112 5.3 Mechanisms of Nucleosome Translocations 115 5.4 Positioning Nucleosomes in the Genome 118 5.5 Gene Regulation via Nucleosome Positioning 124 5.6 Conclusions 127 6 The Folding of the Nucleosome Chain 139 Karsten Rippe 6.1 Introduction 139 6.2 Experimental Systems 140 6.3 Nucleosome–Nucleosome Interactions 142 6.4 DNA Interactions with the Histone Octamer Protein Core 145 6.5 Architectural Chromosomal Proteins and Chromatin States 147 6.6 Chromatin Fiber Conformations 150 6.7 Conclusions 154 7 The Crowded Environment of the Genome 169 Ron Hancock 7.1 Introduction 169 7.2 Basics 169 7.3 Physicochemical Parameters of the Genome’s Environment 171 7.4 Implications of a Crowded Environment for the Conformation of the Interphase Genome 171 7.5 Assembly and Localization of Macromolecular Machines for Genome Transcription and Replication 175 7.6 The Environment of the Genome during Mitosis 177 7.7 Effects of a Crowded Environment on Searching for Targets in the Genome 178 7.8 The Relative Importance of Entropic and Ionic Interactions for the Conformations and Interactions of Macromolecules in the Nucleus 179 7.9 The Evolution of Genomes 180 8 The Nuclear Lamina as a Chromatin Organizer 185 Nikolaj Zuleger and Eric C. Schirmer 8.1 Introduction 185 8.2 Genome Organization with Respect to the Nuclear Periphery 187 8.3 Interactions between NE Proteins and Chromatin Proteins/Chromatin Regulatory Proteins 190 8.4 Mechanisms Directing Changes in Genome Organization during Development 193 8.5 Gene Regulation as a Consequence of Peripheral Positioning 198 8.6 Peripheral Chromatin Organization and Disease 201 8.7 Closing Remarks 203 9 Three-Dimensional Architecture of Genomes 211 Job Dekker 9.1 Introduction 211 9.3 Chromosome Architecture as Seen by 3C-Based Assays 218 9.4 3C-Based Data and Single Cell Observations 226 9.5 Towards an Integrated 3C-Based View of Genome Architecture 227 10 Transcriptional Initiation: Frequency, Bursting, and Transcription Factories 235 Kieran Finan and Peter R. Cook 10.1 Transcription in Mammalian Nuclei 235 10.2 Transcription Is an Infrequent Event 236 10.3 Transcription Is Noisy 238 10.4 What Causes “Bursting”? 245 10.5 Conclusion 250 11 Processing of mRNA and Quality Control 255 Ute Schmidt and Edouard Bertrand 11.1 Introduction 255 11.2 Biosynthesis of Messenger RNA 255 11.3 Nuclear Quality Control 265 11.4 Cytoplasmic Messenger RNA Quality Control: Nonsense-Mediated Decay, No-Go and Non-Stop Decay 268 11.5 Concluding Remarks 273 12 The Nucleolus 279 Saskia Hutten, Belinda J. Westman, Franc-ois-Michel Boisvert, Silvana van Koningsbruggen, and Angus I. Lamond 12.1 Introduction 279 12.2 The Nucleolus and Its DNA 280 12.3 The Nucleolus and RNPs: Temporary Visitors or Permanent Residents? 285 12.4 The Nucleolar Proteome 292 12.5 Concluding Remarks 295 13 Non-Coding RNAs as Regulators of Transcription and Genome Organization 309 Katalin Fejes To´th and Gregory Hannon 13.1 Introduction 309 13.2 Classification of Non-Coding RNAs 311 13.3 Small Regulatory RNAs and Their Diverse Nuclear Functions 314 13.4 ncRNAs in Dosage Compensation 324 13.5 Developmental Regulation of Hox Clusters by Cis- and Trans-Acting ncRNAs 328 13.6 Mechanisms of Transcriptional Regulation by Long ncRNAs 330 13.7 Conclusions 338 14 RNA Networks as Digital Control Circuits of Nuclear Functions 353 John S. Mattick 14.1 Introduction 353 14.2 The Information Content of the Genome 353 14.3 The Hidden Layer of Developmentally Expressed Non-Coding RNAs 354 14.4 RNA Control of Nuclear Functions 355 14.5 RNA as the Adaptor in Digital–Analog Transactions 356 14.6 RNA as the Substrate for Environment–Epigenome Interactions 357 14.7 Conclusion 358 15 DNA Replication and Inheritance of Epigenetic States 365 Armelle Corpet and Genevie`ve Almouzni 15.1 Replication in a Chromatin Context: Basic Issues and Principles 365 15.2 Duplication of Nucleosome Organization 368 15.3 Maintenance of Epigenetic Marks and Post-translational Modifications 375 15.4 Concluding Remarks 383 16 Interplay and Quality Control of DNA Damage Repair Mechanisms 395 Berina Eppink, Jeroen Essers and Roland Kanaar 16.1 Introduction 395 16.2 DNA Repair Pathways 396 16.3 Repairing DSBs 400 16.4 Repair during Replication 404 16.5 Interplay and Quality Control during DNA Damage Repair 409 16.6 Applications of Mechanistic Insight in DNA Repair in Anti-Cancer Treatment 410 17 Higher Order Chromatin Organization and Dynamics 417 Hilmar Strickfaden, Thomas Cremer, and Karsten Rippe 17.1 Introduction 417 17.2 Higher Order Chromatin Organization: From 10-nm Thick Nucleosome Chains to Chromosome Territories 418 17.3 Genome Accessibility 424 17.4 Mobility of Chromosomal Loci and Nuclear Bodies 426 17.5 Mitosis Causes Drastic Changes of Chromosome Territory Proximity Patterns in Cycling Cells 429 17.6 Large-Scale Chromatin Dynamics in Nuclei of Cycling and Post-Mitotic Cells 431 17.7 Considerations on Possible Mechanisms of Large-Scale Chromatin Dynamics 434 18 The Mitotic Chromosome: Structure and Mechanics 449 John F. Marko 18.1 Introduction 449 18.2 Structural Components of Mitotic Chromosomes 450 18.3 Large-Scale Organization of Mitotic Chromosomes 457 18.4 Mechanics of Mitotic Chromosomes 459 18.5 Molecular Connectivity of Mitotic Chromosomes 465 18.6 A Model for Mitotic Chromosome Structure and Function 468 18.7 Open Questions 474 19 Meiotic Chromosome Dynamics 487 Nancy Kleckner, Liangran Zhang, Beth Weiner, and Denise Zickler 19.1 Introduction 487 19.2 Recombination at the DNA Level 494 19.3 Coordination between Recombination and Chromosome Dynamics 500 19.4 Homologous Chromosome Pairing 507 19.5 Meiotic Recombination as a Paradigm for Spatial Patterning along Chromosomes 515 20 Understanding Genome Function: Quantitative Modeling of Chromatin Folding and Chromatin-Associated Processes 535 Mariliis Tark-Dame, Martijn S. Luijsterburg, Dieter W. Heermann and Roel van Driel 20.1 Modeling of Genome Functioning 535 20.2 Large-Scale Chromatin Folding 536 20.3 Assembly of Chromatin-Associated Multiprotein Complexes 543 20.4 Outlook 548 Index 557
Karsten Rippe leads the Research Group Genome Organization & Function at the German Cancer Research Center and the BioQuant Institute in Heidelberg, Germany. In his research, he combines molecular/cell biology and physics to quantitatively investigate and model the relation between nuclear DNA organization and cell function. Karsten Rippe has obtained his academic degrees from the University of Gottingen while working at the Max Planck Institute for Biophysical Chemistry and continued his scientific career at the University of Oregon in Eugene and the Kirchhoff-Institut fur Physik in Heidelberg. He has authored more than 80 scientific publications in the fields of DNA structure, transcription and chromatin and has received several scientific awards, including the Otto Hahn medal of the Max Planck Society and the European Beckman DNA Award.
By way of its clear and logical structure, as well as abundant highresolution illustrations, this is a systematic survey of the players and pathways that control genome function in the mammalian cell nucleus. As such, this handbook and reference ties together recently gained knowledge from a variety of scientific disciplines and approaches, dissecting all major genomic events: transcription, replication, repair, recombination and chromosome segregation. A special emphasis is put on transcriptional control, including genome-wide interactions and non-coding RNAs, chromatin structure, epigenetics and nuclear organization. With its focus on fundamental mechanisms and the associated biomolecules, this will remain essential reading for years to come.

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