Genome Organization And Function In The Cell Nucleus

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.

Table of Contents:
Preface DECIPHERING DNA SEQUENCE INFORMATION Introduction Genes and Transcribed Regions Non-Coding Genomic Elements Regulatory Information Individual Genetic Polymorphisms and Their Effect on Gene Expression Conclusion DNA METHYLATION Introduction Eukaryotic DNA Methyltransferases Distribution of 5-Methylcytosine in the Mammalian Genome Control of Gene Exression by DNA Methylation DNA Demethylation NUCLEOSOMES AS CONTROL ELEMENTS FOR ACCESSING THE GENOME Introduction and Basic Terminology Nucleosomes are the Building Blocks of Chromatin Nucleosomes are Dynamic Macromolecular Assemblies Histone Variants and Their Effect on Nucleosome Structure and Dynamics Histone Modifications in Nucleosome and Chromatin Structure DNA Sequence and Nucleosome Positioning Histone Chaperones and Chromatin Dynamics Outlook and Concluding Remarks HISTONE MODIFICATIONS AND THEIR ROLE AS EPIGENETIC MARKS The Complexity of Histone Modifications Regulating Histone Modifications in Chromatin The "Histone Code" Hypothesis Exploiting the Complexity of the Histone Code: "Crosstalk" Between Different Modifications Are Histone Modifications Heritable Epigenetic Marks? Conclusions CHROMATIN REMODELING AND NUCLEOSOME POSITIONING Introduction Chromatin Remodeling Complexes Mechanisms of Nucleosome Translocations Positioning Nucleosomes in the Genome Gene Regulation via Nucleosome Positioning Conclusions THE FOLDING OF THE NUCLEOSOME CHAIN Introduction Experimental Systems Nucleosome-Nucleosome Interactions DNA Interactions with the Histone Octamer Protein Core Architectural Chromosomal Proteins and Chromatin States Chromatin Fiber Conformations Conclusions THE CROWDED ENVIRONMENT OF THE GENOME Introduction Basics Physicochemical Parameters of the Genome's Environment Implications of a Crowded Environment for the Conformation of the Interphase Genome Assembly and Localization of Macromolecular Machines for Genome Transcription and Replication The Environment of the Genome during Mitosis Effects of a Crowded Environment on Searching for Targets in the Genome The Relative Importance of Entropic and Ionic Interactions for the Conformations and Interactions of Macromolecules in the Nucleus The Evolution of Genomes THE NUCLEAR LAMINA AS A CHROMATIN ORGANIZER Introduction Genome Organization with Respect to the Nuclear Periphery Interactions between NE Proteins and Chromatin Proteins/Chromatin Regulatory Proteins Mechanisms Directing Changes in Genome Organization during Development Gene Regulation as a Consequence of Peripheral Positioning Peripheral Chromatin Organization and Disease Closing Remarks THREE-DIMENSIONAL ARCHITECTURE OF GENOMES Introduction 3C-Based Methods to Study Chromosome Architecture Chromosome Architecture as Seen by 3C-Based Assays 3C-Based Data and Single Cell Observations Towards an Integrated 3C-Based View of Genome Architecture TRANSCRIPTIONAL INITIATION: FREQUENCY, BURSTING, AND TRANSCRIPTION FACTORIES Transcription in Mammalian Nuclei Transcription Is an Infrequent Event Transcription is Noisy What Causes "Bursting"? Conclusion PROCESSING OF mRNA AND QUALITY CONTROL Introduction Biosynthesis of Messenger RNA Nuclear Quality Control Cytoplasmic Messenger RNA Quality Control: Nonsense-Mediated Decay, No-Go and Non-Stop Decay Concluding Remarks THE NUCLEOLUS Introduction The Nucleolus and Its DNA The Nucleolus and RNPs: Temporary Visitors or Permanent Residents? The Nucleolar Proteome Concluding Remarks NON-CODING RNAs AS REGULATORS OF TRANSCRIPTION AND GENOME ORGANIZATION Introduction Classification of Non-Coding RNAs Small Regulatory RNAs and Their Diverse Nuclear Functions ncRNAs in Dosage Compensation Developmental Regulation of Hox Clusters by Cis- and Trans-Acting ncRNAs Mechanisms of Transcriptional Regulation by Long ncRNAs Conclusions RNA NETWORKS AS DIGITAL CONTROL CIRCUITS OF NUCLEAR FUNCTIONS Introduction The Information Content of the Genome The Hidden Layer of Developmentally Expressed Non-Coding RNAs RNA Control of Nuclear Functions RNA as the Adaptor in Digital-Analog Transactions RNA as the Substrate for Environment-Epigenome Interactions Conclusion DNA REPLICATION AND INHERITANCE OF EPIGENETIC STATES Replication in a Chromatin Context: Basic Issues and Principles Duplication of Nucleosome Organization Maintenance of Epigenetic Marks and Post-Translational Modifications Concluding Remarks INTERPLAY AND QUALITY CONTROL OF DNA DAMAGE REPAIR MECHANISMS Introduction DNA Repair Pathways Repairing DSBs Repair During Replication Interplay and Quality Control During DNA Damage Repair Applications of Mechanistic Insight in DNA Repair in Anti-Cancer Treatment HIGHER ORDER CHROMATIN ORGANIZATION AND DYNAMICS Introduction Higher Order Chromatin Organization: From 10-nm Thick Nucleosome Chains to Chromosome Territories Genome Accessibility Mobility of Chromosomal Loci and Nuclear Bodies Mitosis Causes Drastic Changes of Chromosome Territory Proximity Patterns in Cycling Cells Large-Scale Chromatin Dynamics in Nuclei of Cycling and Post-Mitotic Cells Considerations on Possible Mechanisms of Large-Scale Chromatin Dynamics THE MITOTIC CHROMOSOME: STRUCTURE AND MECHANICS Introduction Structural Components of Mitotic Chromosomes Large-Scale Organization of Mitotic Chromosomes Mechanics of Mitotic Chromosomes Molecular Connectivity of Mitotic Chromosomes A Model for Mitotic Chromosome Structure and Function Open Questions MEIOTIC CHROMOSOME DYNAMICS Introduction Recombination at the DNA Level Coordination between Recombination and Chromosome Dynamics Homologous Chromosome Pairing Meiotic Recombination as a Paradigm for Spatial Patterning along Chromosomes UNDERSTANDING GENOME FUNCTION: QUANTITATIVE MODELING OF CHROMATIN FOLDING AND CHROMATIN-ASSOCIATED PROCESSES Modeling of Genome Functioning Large-Scale Chromatin Folding Assembly of Chromatin-Associated Multiprotein Complexes Outlook