Nuclear Pore Complexes in Genome Organization, Function and Maintenance

The three-dimensional organization of the DNA inside the eukaryotic cell nucleus has emerged a critical regulator of genome integrity and function. Increasing evidence indicates that nuclear pore complexes (NPCs), the large protein channels that connect the nucleus to the cytoplasm, play a critical role in the establishment and maintenance of chromatin organization and in the regulation of gene activity. These findings, which oppose the traditional view of NPCs as channels with only one: the facilitation of nucleocytoplasmic molecule exchange, have completely transformed our understanding of these structures. This book describes our current knowledge of the role of NPCs in genome organization and gene expression regulation. It starts by providing an overview of the different compartments and structures of the nucleus and how they contribute to organizing the genome, then moves to examine the direct roles of NPCs and their components in gene expression regulation in different organisms, and ends by describing the function of nuclear pores in the infection and genome integration of HIV, in DNA repair and telomere maintenance, and in the regulation of chromosome segregation and mitosis. This book provides an intellectual backdrop for anyone interested in understanding how the gatekeepers of the nucleus contribute to safeguarding the integrity and function of the eukaryotic genome.

Auteur

Maximiliano D'Angelo, Ph.D., is Faculty of the Development, Aging and Regeneration Program and the Immunity and Pathogenesis Program at the Sanford Burnham Medical Discovery Institute in La Jolla, California. He is also member of the Tumor Initiation and Maintenance Program of the NCI-designated Cancer Center. Before moving to SBP, Dr. D'Angelo was a Principal investigator of the Cardiovascular Research Institute at the University of California San Francisco and Assistant Professor of the Department of Biochemistry & Biophysics. Dr. D'Angelo received his Ph.D. in molecular biology from the University of Buenos Aires, Argentina, and trained at The Scripps Research Institute and the Salk Institute for Biological before beginning his independent career. He has been Fellow of the Ellison Foundation and American Federation for Aging Research, Pew Latin American Fellow, Pew Biomedical Scholar and Scholar of the American Cancer Society.

Contenu
Nuclear Pore Complexes In The Regulation Of Genome Organization And Gene Expression

Contents:

1. Spatial Organization Of The Nucleus Compartmentalizes And Regulates The Genome Michael I. Robson, Andrea Rizzotto, and Eric C. Schirmer

1.1 Introduction

1.2 Subdomains of the nucleus 1.2.1 Nuclear Envelope

1.2.2 Nuclear pore complexes

1.2.3 Chromosomes 1.2.4 Centromeres

1.2.5 Telomeres

1.2.6 Nucleolus 1.2.7 Perinucleolar compartment

1.2.8 Cajal bodies

1.2.9 Gemini of coiled bodies 1.2.10 PML/ND10 bodies

1.2.11 Speckles

1.2.12 Paraspeckles 1.2.13 Histone bodies

1.2.14 Polycomb bodies

1.3 Composition of nuclear structures 1.4 Self-assembly of nuclear structures

1.5 Genome organization patterns

1.5.1 Loops and topologically-associated domains

1.5.2 Compartments

1.6 Structure-function relationships

1.6.1 Layers of functional separation

1.6.2 Loops

1.6.3 Scaffolds

1.6.4 Boundary elements

1.7 General versus tissue- or state-specific functions

1.8 Conclusions and open questions

1.9 References

2. The Molecular Composition And Function Of The Nuclear Periphery And Its Impact On The Genome

C. Patrick Lusk and Megan C. King

2.1 The conservation of the spatial positioning of the genome across eukaryotes

2.2 Integral INM proteins

2.3 A brief history of INM targeting

2.4 The nuclear lamina

2.5 Lamina Associated Domains

2.6 LADs as developmentally regulated regions

2.7 Histone modifications at the nuclear periphery

2.8 Peripheral tethers

2.9 Lamina Associated Sequences

2.10 Beyond silencing: the periphery and genome integrity

2.11 Repetitive DNA and the nuclear periphery

2.12 Inputs of nuclear compartmentalization on DNA repair mechanisms

2.13 Outlook

2.14 References

3. Nuclear Pore Complexes: Fascinating Nucleocytoplasmic Checkpoints

Victor Shahin

3.1 Introduction

3.2 Versatility of the NPCs structural configuration

3.3 Composition, heterogeneity and dynamics of the NPCs

3.4 NPCs as fascinating gatekeepers between the cytoplasm and the nucleus

3.5 Configuration and functional mechanisms of the selective NPC barrier: FG-Nups

3.6 References

4. Nuclear Pore Complex In Genome Organization And Gene Expression In Yeast

Carlo Randise-Hinchliff and Jason H Brickner

4.1 Introduction

4.2 Spatial organization of the yeast genome 4.3 Composition of NPC

4.4 Nuclear pore complex interacts with the genome

4.5 Nups influence transcription 4.6 Mechanisms of Gene recruitment

4.7 Interchromosomal clustering at the NPC

4.8 Regulation of gene recruitment and clustering

4.9 Gene recruitment and clustering through the cell cycle

4.10 Transcription Memory

4.11 Molecular mechanism of INO1 transcriptional memory

4.12 Concluding Remarks

4.13 References

5. Nuclear Pore Complex In Genome Organization And Gene Expression In Drosophila

Terra Kuhn and Maya Capelson

5.1 Introduction

5.2 Unique features of Drosophila NPC structure and assembly

5.3 Phenotypes of Drosophila Nups

5.3.1 Components of the Nup107-160 sub-complex in Drosophila speciation 5.3.2 NPC components and ALS/FTD pathog...