Note: Intro -- Contents -- Part I: Nuclear Periphery -- Human Diseases Related to Nuclear Envelope Proteins -- 1 Introduction to the Nuclear Envelope -- 2 Nuclear Membranes -- 2.1 Inner Nuclear Membrane -- 2.2 Outer Nuclear Membrane -- 3 Perinuclear Space -- 4 Nuclear Pore Complex -- 5 Nuclear Lamina -- 5.1 A-type Lamins -- 5.1.1 Striated Muscle -- 5.1.2 Lipodystrophy -- 5.1.3 Peripheral Neuropathy -- 6 Multisystem Disorders -- 6.1 B-type Lamins -- 7 Conclusions -- References -- Part II: Nuclear Bodies -- The Nucleolus: Structure and Function -- 1 Introduction -- 2 The Nucleolar Organisation -- 2.1 Nucleolar Organiser Regions (NORs) -- 2.2 rDNA Transcription -- 2.3 Processing of rRNA and Ribosome Assembly -- 3 Other Functions for the Nucleolus -- 3.1 RNA Complexity in the Nucleolus -- 3.2 Mitosis and Cell Cycle Regulation -- 3.3 Stress Sensor -- 4 The Nucleolus and Diseases -- 4.1 Cancer and Genomic Instability -- 4.2 Viral Infections -- 4.3 Neurodegenerative Disorders -- 5 Summary -- References -- Pre-mRNA Splicing and Disease -- 1 Introduction -- 1.1 The Discovery of Splicing -- 1.2 The Splicing Reaction -- 1.3 The Splicing Code -- 1.4 Co-transcriptional Nature of Splicing -- 1.5 Splicing Factor Compartments -- 2 Extent and Regulation of Alternative Splicing -- 2.1 First Discoveries of Alternative Splicing -- 2.2 Modes of Alternative Splicing -- 2.3 Regulation of Alternative Splicing Through Splicing Enhancers and Silencers -- 2.4 Effects of Transcription, Promoters and Chromatin on Alternative Splicing -- 2.5 Integration of Splicing into Cell Signaling and Regulatory Networks -- 2.6 Extent of Alternative Splicing Genome-Wide and Conservation Across Species -- 3 Pre-mRNA Splicing and Disease -- 3.1 Nature and Frequency of Splicing Mutations -- 3.2 Examples of Aberrant Splicing in Cancer -- 3.3 Examples of Aberrant Splicing in Other Diseases. , 3.4 Manipulating Splicing in Therapy -- 4 Summary -- References -- Acute Promyelocytic Leukaemia: Epigenetic Function of the PML-RARα Oncogene -- 1 Acute Promyelocytic Leukaemia -- 2 The PML-RARα Oncogene -- 2.1 PML -- 2.2 RARα -- 2.3 Pharmacological Targeting of PML-RARα Leads to Disease Remission -- 2.4 PML-RARα Mouse Models -- 2.5 PML-RARα Mechanisms of Action -- 3 PML-RARα Epigenetic Function -- 3.1 Histone Modifications -- 3.1.1 Histone Acetylation -- 3.1.2 Histone Methylation -- 3.2 Chromatin-Remodelling Factors and Histone Variants -- 3.3 DNA Methylation -- 4 Is Chromatin Remodelling a Viable Option for APL Therapy? -- 5 Conclusions and Outstanding Questions -- Box 1: Epigenetics -- References -- Part III: Chromosomes -- Spatial Genome Organization and Disease -- 1 Introduction -- 2 Non-random Genome Organization -- 2.1 Spatial Separation of Gene-Rich and Gene-Poor Genomic Regions -- 2.2 A Link Between Gene Activity and Positioning -- 2.3 Beyond Gene Expression -- 3 Genome Organization and Disease -- 3.1 The Nuclear Envelope, Laminopathies and Genome Organization -- 3.2 Altered Genome Organization in Other Non-cancerous Diseases -- 3.3 Altered Genome Organization in Cancer -- 4 The Role of Positioning and Chromatin in Translocation Formation -- 4.1 Spatial Proximity of Translocation Partners -- 4.2 Chromatin Organization and Translocations -- 5 Summary -- References -- Telomeres and Chromosome Stability -- 1 Discovery of Telomeres -- 2 Telomere: Structure and Function -- 3 Telomere-Associated Proteins -- 3.1 Shelterin Complex -- 3.2 Roles of the Shelterin Complex at the Telomeres: T-Loop Maintenance, Telomere Length Regulation and Suppression of DDR -- 3.3 The CST Complex -- 4 Telomere Length Maintenance -- 4.1 Enzyme-Based Telomere Maintenance: Telomerase -- 4.2 Telomerase Structure -- 4.3 Telomerase Regulation. , 4.4 Homologous Recombination Based: Alternative Lengthening of Telomeres (ALT) -- 4.5 Characteristics of ALT Cells -- 4.6 Factors Regulating ALT -- 4.7 ALT in Human Cancer -- 5 Telomeres and Epigenetics -- 6 Nuclear Organization and Telomeres -- 7 Telomere and Disease -- 7.1 Telomeres and Aging -- 7.2 Telomeres and Cancer -- 8 Concluding Remarks -- References -- Part IV: Nuclear Domains and Development -- Polycomb Bodies -- 1 Nuclear ``Bodies´´ -- 2 Polycomb Complexes and Their Genomic Function -- 3 Evidence for PcG Foci from Nuclear Imaging Studies -- 4 Transgene-Dependent Evidence -- 5 The Involvement of the RNAi Machinery -- 6 The Assembly and Behavior of Polycomb Bodies -- 7 Chromosome Conformation Capture and Nuclear Architecture -- 8 Comparing Conformation Capture and Imaging Studies -- 9 Role of PRC1 Components -- 10 SUMO and Polycomb Body Formation -- 11 A Synthesis? -- References -- The Continuing Flight of Ikaros -- 1 The Diverse Functions of Ikaros -- 2 Ikaros Family and Structure -- 3 Ikaros DNA-Binding Specificity -- 4 Ikaros and the Chromatin Landscape -- 5 Lineage Specificity of Ikaros Activity -- 6 Ikaros in Early Hematopoiesis -- 7 Ikaros and Early B-Cell Development -- 8 Ikaros in T-Cell Development and Function -- 9 T-Cell Progenitors -- 10 Mature T-Cell Function -- 11 Ikaros and the Immune Response -- 12 Ikaros and Notch -- 13 Ikaros and the Three-Dimensional Organization of Chromatin -- 14 Role of Ikaros Family Members in Non-hematopoietc Tissues -- 15 Regulation of Ikaros Activity -- 16 Ikaros and Leukemogenesis -- 17 Evolution of the Ikaros Family -- 18 Future Challenges -- References -- Part V: Nuclear Domains and Cell Stress -- Senescence Associated Heterochromatic Foci: SAHF -- 1 Introduction -- 1.1 Cellular Senescence -- 1.2 Chromatin and Senescence -- 2 Senescence Associated Heterochromatic Foci (SAHF). , 2.1 A Model System for Chromatin Dynamics -- 2.2 SAHF Show Spatial Segregation and Clustering of Repressive Chromatin Marks -- 2.3 Replication Timing -- 2.4 Histone Variants and Modifications -- 2.5 Architectural Proteins: HMGA1/2 -- 2.6 Chromosomal Territories -- 2.7 Xi and SAHF -- 2.8 Histone Chaperones -- 2.9 Lamin Associated Domains in SAHF Formation -- 2.10 Ultrastructural Studies on SAHF Link Senescence and Progeria -- 2.11 SAHF Function -- References -- DNA Repair Foci Formation and Function at DNA Double-Strand Breaks -- 1 Introduction -- 1.1 The Hierarchical Nature of DNA Double-Strand Break (DSB) Repair -- 2 What Do We Know About the Structure of DNA Repair Foci (DRF)? -- 2.1 Ultrastructure of DRFs -- 2.2 How Do DRFs Assemble? -- 2.3 DRF Protein Composition and Dynamics -- 2.4 Intranuclear Mobility of DRFs -- 3 What Is the Relationship Between DNA Damage Response and Repair Proteins and the DNA Sequences Found in DRFs? -- 3.1 Why Are So Many Copies of Proteins Assembled at Sites of DRFs? -- 4 Summary -- References -- Nuclear Domains and DNA Repair -- 1 Introduction -- 2 The Nuclear Lamina and DNA Repair -- 2.1 The Role of Inner Nuclear Membrane Proteins in DNA Repair -- 2.2 DDR and DNA Repair at the Nuclear Lamina -- 3 Promyelocytic Leukemia Nuclear Bodies (PML NBs) and DNA Repair -- 3.1 PML NB Composition and Functions -- 3.2 Multiple Roles of PML and PML NBs in the DNA Damage Response -- 3.2.1 Roles for PML in Regulating DNA Damage-Induced Cell Cycle Checkpoints -- 3.2.2 DNA Repair Factors and Persistent DNA Lesions Associate with PML NBs -- 3.2.3 Role for PML in DNA Repair by Homologous Recombination -- 4 Summary -- References -- The Interplay Between Inflammatory Signaling and Nuclear Structure and Function -- 1 Introduction -- 1.1 Inflammation -- 1.2 Cancer-Related Inflammation -- 2 DNA Damage Response and Pro-Inflammatory Signaling. , 2.1 Reactive Oxygen and Nitrogen Species -- 2.2 NFkappaB Pathway -- 2.3 Role of p38-MAPK in Activation of Pro-Inflammatory Cytokines -- 3 The Impact of Pro-Inflammatory Signaling Pathways on Nuclear Structure and Function -- 3.1 DNA Damage Induced by Pro-Inflammatory Cytokines -- 3.1.1 IL1 -- 3.1.2 IL6 -- 3.1.3 IL8 -- 3.1.4 TGFbeta -- 3.1.5 TNFα -- 3.2 Structural Changes in Nucleus Induced by Pro-Inflammatory Cytokines -- 3.2.1 Chromatin Structure -- 3.2.2 Nuclear Compartments -- Nuclear Lamina -- PML Nuclear Bodies -- 3.3 Secondary ``Bystander´´ Senescence -- 4 Summary -- References -- Manipulation of PML Nuclear Bodies and DNA Damage Responses by DNA Viruses -- 1 Introduction -- 2 DNA Viruses and PML Nuclear Bodies -- 2.1 Antiviral Function of PML Nuclear Bodies -- 2.2 Mechanisms of Disruption of PML NBs -- 2.3 Herpes Simplex and Varicella-Zoster Viruses -- 2.4 Cytomegalovirus -- 2.5 Epstein-Barr Virus -- 2.6 Kaposi´s Sarcoma-Associated Herpesvirus, Gammaherpesvirus 68 and Herpesvirus Saimiri -- 2.7 Adenovirus -- 3 DNA Viruses and DNA Damage Responses -- 3.1 Herpes Simplex Virus -- 3.2 Cytomegalovirus -- 3.3 Epstein-Barr Virus -- 3.4 KSHV -- 3.5 Adenovirus -- 3.6 Polyomaviruses -- 3.7 Papillomaviruses -- 4 Summary -- References -- Part VI: Macromolecular Dynamics Within the Nucleus -- Energy-Dependent Intranuclear Movements: Role of Nuclear Actin and Myosins -- 1 Introduction -- 1.1 Actin and Myosin-Based Motility in the Cytoplasm -- 2 Evidence Supporting the Existence of Nuclear Actin and Myosins -- 3 Actin and Myosin in Transcription: Movement on the Gene? -- 4 Long Range Movements in the Nucleus Using Actin and Myosins -- 5 Summary -- References -- Nucleosome Dynamics Studied by Förster Resonance Energy Transfer -- 1 Introduction -- 2 Förster Resonance Energy Transfer (FRET). , 2.1 Experimental Determination of Energy Transfer and Interdye Distances.