Advances in Nuclear Architecture

1. Auflage 2010
ISBN: 978-90-481-9899-3
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 210 Seiten

This book provides a snapshot of the state-of-the art in the study of mammalian cell nuclear architecture, and features a diverse range of chapters written by top researchers. A key aspect is an emphasis on precise and repeatable quantitative analysis and simulation in addition to the more familiar biological perspective. The fusion of such material frames the future of the discipline. Quantitative contributions stress reproducible and robust 3D analysis, using a variety of tools ranging from point pattern analysis to shape registration methods. Biological insights include the role of nuclear subdomains in cancer, nuclear molecular motors, and a holistic view of gene transcription.

Autoren/Hrsg.

Inhaltsverzeichnis

1;Foreword;6
2;Contents;8
3;Chapter 1: Nuclear Subdomains and Cancer;10
3.1;1.1 Introduction;13
3.2;1.2 Promyelocytic Leukemia Nuclear Bodies and Tumour Suppression;17
3.2.1;1.2.1 PML Plays a Role in Multiple Tumour Suppressor Pathways;19
3.2.1.1;1.2.1.1 The Regulation of p53 Function by PML: A Paradigm for PML NB Function in Tumour Suppression;19
3.2.1.2;1.2.1.2 PML NBs and the Response to Genotoxic Stress;23
3.2.1.3;1.2.1.3 PML Controls Cellular Fate by Mediating Apoptosis and Cellular Senescence;25
3.2.2;1.2.2 Pathways Regulating PML Protein Stability Represent Possible Therapeutic Targets for Cancer Treatment;29
3.2.2.1;1.2.2.1 Regulation of PML Protein Stability by Sumoylation;29
3.2.2.2;1.2.2.2 Regulation of PML Protein Stability by Phosphoryation;31
3.2.3;1.2.3 Summary of PML NBs and Cancer;32
3.3;1.3 The Nucleolus and Cancer;33
3.3.1;1.3.1 AgNOR Scores as a Prognostic Indicator in Cancer;35
3.3.2;1.3.2 Nucleolar Function, Ribosome Biogenesis and the Inter-Regulation of Cell Growth and Proliferation;36
3.3.3;1.3.3 Nucleolar Functions Beyond Ribosome Production;38
3.3.3.1;1.3.3.1 The Nucleolus, p53, ARF, and the Cell Stress Response;39
3.3.3.2;1.3.3.2 Nucleostemin;40
3.3.3.3;1.3.3.3 Nucleophosmin;41
3.3.3.4;1.3.3.4 Nucleolin;41
3.3.3.5;1.3.3.5 Other Tumour Suppressors;42
3.3.3.6;1.3.3.6 The Nucleolus and Genome Maintenance;42
3.3.4;1.3.4 Nucleolar Function as a Cancer Initiator;44
3.3.5;1.3.5 Summary of the Nucleolus and Cancer;45
3.4;1.4 The Perinucleolar Compartment in Cancer Cells;46
3.4.1;1.4.1 The PNC Formation is Associated with Malignant Phenotype In Vitro and In Vivo;47
3.4.2;1.4.2 Association of PNC with Pol III Transcription;48
3.4.3;1.4.3 The PNC is Nucleated upon DNA;49
3.5;1.5 Evidence for the Coordination of Function Between Nuclear Subdomains in Tumour Suppression;50
3.6;1.6 Concluding Remarks;53
3.7;References;53
4;Chapter 2: Spatial Point Process Analysis of Promyelocytic Leukemia Nuclear Bodies;68
4.1;2.1 Introduction;68
4.2;2.2 Spatial Point Processes: Theory, Models and Statistics;71
4.3;2.3 Spatial Point Process: Definitions and Calculations;71
4.4;2.4 Binomial and Poisson Point Processes;72
4.4.1;2.4.1 The Binomial Point Process;72
4.4.2;2.4.2 The Homogeneous Poisson Point Process;73
4.4.3;2.4.3 Inhomogeneous Poisson Point Process;74
4.4.4;2.4.4 Estimating Intensity;74
4.4.5;2.4.5 Edge-Effects;75
4.5;2.5 Testing for Spatial Point Processes;75
4.5.1;2.5.1 The Empty Space Function F;75
4.5.2;2.5.2 The Nearest Neighbour Distribution Function G;76
4.5.3;2.5.3 The Pair Correlation Function g;76
4.5.4;2.5.4 The K Function;77
4.5.5;2.5.5 Relationships Between Spatial Point Process Functions;77
4.6;2.6 More Complicated Point Process Models;78
4.6.1;2.6.1 Gauss–Poisson Process;79
4.6.2;2.6.2 Matérn Cluster Process;79
4.6.3;2.6.3 Markov Point Processes;80
4.6.4;2.6.4 Cox Processes;80
4.7;2.7 Marked Spatial Point Processes;81
4.8;2.8 Bivariate Spatial Point Process Analysis of PML NBsand RNA Polymerase II;82
4.9;2.9 A Marked Inhomogeneous Poisson Process Model for PML;84
4.10;2.10 Conclusion;90
4.11;Appendix;92
4.12;References;93
5;Chapter 3: Quantitative Approaches to Nuclear Architecture Analysis and Modelling;95
5.1;3.1 Introduction;96
5.2;3.2 Experimental Evidence for Nuclear Genome Large Scale Architecture;97
5.3;3.3 Quantitative Microscopy of Nuclear Genome Architecture;98
5.4;3.4 Quantitative Modeling of Nuclear Genome Large Scale Architecture;102
5.5;3.5 Application of the SCD Computer Model to Predict Cell Type Specific Radiation-Induced Chromosomal Aberrations;106
5.6;3.6 Extension of the SCD Model of Large Scale Nuclear Genome Architecture to Simulate Interactions with Other Nuclear Bodies;111
5.6.1;3.6.1 SCD model and banding pattern;113
5.6.2;3.6.2 Calibration;115
5.6.3;3.6.3 Comparison with Experimental Observations;117
5.7;3.7 The Dynamics of Large Scale Nuclear Genome Structure in the Human Cell Nucleus;118
5.8;3.8 Towards Quantitative Analysis of Nuclear Genome Nanostructure I: Computer Models;122
5.9;3.9 Towards Quantitative Analysis of Nuclear Genome Nanostructure II: Perspectives of Superresolution Light Microscopy;125
5.9.1;3.9.1 Perspectives;131
5.10;References;132
6;Chapter 4: Statistical Shape Theory and Registration Methods for Analyzing the 3D Architecture of Chromatin in Interphase Cell Nuclei;138
6.1;4.1 Introduction;139
6.2;4.2 Image Data and Computational Methods;141
6.2.1;4.2.1 Image Data;141
6.2.2;4.2.2 Uniformity Test;142
6.2.3;4.2.3 Triangulation;143
6.2.4;4.2.4 Point-Based Rigid Registration;143
6.2.5;4.2.5 Investigation of the Statistical Distribution Using Kendall’s Spherical Coordinates;144
6.2.6;4.2.6 Statistical Shape Modeling Using the Fisher Distribution;144
6.2.7;4.2.7 Quantitative Analysis of the Correlation Between the Shapes of the Active and Inactive X-Chromosomes;145
6.2.8;4.2.8 Spatial Normalization of Cell Nuclei Using Non-rigid Registration;145
6.3;4.3 Experimental Results;146
6.4;4.4 Discussion;151
6.5;References;152
7;Chapter 5: Nuclear Molecular Motors for Active, Directed Chromatin Movement in Interphase Nuclei;155
7.1;5.1 Molecular Motors;155
7.2;5.2 The Dynamic Nucleus;157
7.3;5.3 Acto: Myosin Molecular Motors in Nuclei;158
7.3.1;5.3.1 Nuclear Actin and Actin-Related Proteins;158
7.3.2;5.3.2 Nuclear Myosins;160
7.3.2.1;5.3.2.1 Nuclear Myosin 1b (NMIb);161
7.3.2.2;5.3.2.2 Distribution of NM1b;162
7.4;5.4 Nuclear Motor Protein Involvement in Long Range Movement of Chromatin;164
7.4.1;5.4.1 Activated Gene Loci Movement in Real Time;165
7.4.2;5.4.2 Exogenous Plasmid Intranuclear Movements Use the Host Cells’ Nuclear Actin;166
7.4.3;5.4.3 Rapid Repositioning of Whole Chromosome Territories;167
7.4.4;5.4.4 Active Chromosomal Movement Towards a Specific Nuclear Entity;169
7.4.5;5.4.5 Long Range Chromatin Movement to the Nuclear Periphery in Yeast;170
7.5;5.5 Future Perspectives;171
7.6;References;173
8;Chapter 6: Methodology for Quantitative Analysis of 3-D Nuclear Architecture;179
8.1;6.1 Introduction;180
8.2;6.2 Segmentation of CLSM Image Data;181
8.3;6.3 Investigating Nuclear Architecture;185
8.3.1;6.3.1 Radial Analysis;186
8.3.2;6.3.2 Co-Localisation Analysis;186
8.3.3;6.3.3 Distance-Based Analysis;187
8.3.4;6.3.4 Spatial Point Pattern Analysis;187
8.4;6.4 The Future of Analysing Nuclear Architecture – Image Registration?;189
8.5;6.5 Conclusion;191
8.6;References;191
9;Chapter 7: Thinking Holistically About Gene Transcription;194
9.1;7.1 Introduction;194
9.2;7.2 The Nucleus;195
9.3;7.3 Transcription Factories;196
9.4;7.4 Gene Networks;197
9.5;7.5 Organization in the Chromatin Compartment;200
9.6;7.6 Global Nuclear Organization;202
9.7;7.7 Modelling Gene Expression;206
9.8;References;208
10;Index;211