Regulation of Nuclear Organization and Function

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 17615

Special Issue Editor

Andalusian Center for Developmental Biology (CABD), Spanish Research Council, Universidad Pablo de Olavide, Sevilla, Spain
Interests: nuclear envelope; nuclear pore complex; laminopathies; aging; nuclear organization; chromatin structure and function; gene regulation; chromosome segregation; nucleocytoplasmic transport; live microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Precise regulation of which genes are expressed when and to which level is pivotal to all cellular forms of life. During development from zygote to mature organism, a complex transcriptional program unfolds where genes are activated and silenced in a highly orchestrated manner. Perturbations to gene expression can therefore have dramatic consequences on organismal growth and health. In eukaryotes, gene expression is controlled at multiple levels from the spatial organization of genes within the cell nucleus to nucleosome positioning and access of transcription factors. This Special Issue will cover novel findings on themes concerning nuclear organization and function. This embraces the three-dimensional organization of the genome, including global segregation of eu- and heterochromatin, phase separation, and folding of topologically associated domains and loops that facilitate interactions between regulatory elements of the genome. Access of transcription factors to target genes is often regulated by their nucleocytoplasmic distribution, but is also sensitive to posttranscriptional modifications of histones, which, together with nucleosome positioning, determine the compactness of chromatin. Finally, enrichment or anchoring of particular genes at nuclear features such as the nucleolus, the nuclear lamina, or nuclear pore complexes can have profound effects on their expression as well as DNA replication and repair kinetics. The Special Issue in particular invites contributions that cover advances in single-cell omics and novel multiplex imaging techniques to analyze cell and tissue heterogeneity.

Dr. Peter Askjaer
Guest Editor

Manuscript Submission Information

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Keywords

  • Epigenetics
  • Euchromatin
  • Gene expression
  • Heterochromatin
  • Imaging
  • Nuclear envelope
  • Nuclear lamina
  • Nuclear pore complex
  • Single-cell omics
  • Topologically associating domains (TADs)

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Published Papers (6 papers)

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Research

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21 pages, 3700 KiB  
Article
An Inducible System for Silencing Establishment Reveals a Stepwise Mechanism in Which Anchoring at the Nuclear Periphery Precedes Heterochromatin Formation
Cells 2021, 10(11), 2810; https://doi.org/10.3390/cells10112810 - 20 Oct 2021
Cited by 1 | Viewed by 1719
Abstract
In eukaryotic cells, silent chromatin is mainly found at the nuclear periphery forming subnuclear compartments that favor silencing establishment. Here, we set up an inducible system to monitor silencing establishment at an ectopic locus in relation with its subnuclear localization in budding yeast. [...] Read more.
In eukaryotic cells, silent chromatin is mainly found at the nuclear periphery forming subnuclear compartments that favor silencing establishment. Here, we set up an inducible system to monitor silencing establishment at an ectopic locus in relation with its subnuclear localization in budding yeast. We previously showed that introducing LacI bound lacO arrays in proximity to gene flanked by HML silencers favors the recruitment of the yeast silencing complex SIR at this locus, leading to its silencing and anchoring at the nuclear periphery. Using an inducible version of this system, we show that silencing establishment is a stepwise process occurring over several cell cycles, with the progressive recruitment of the SIR complex. In contrast, we observed a rapid, SIR-independent perinuclear anchoring, induced by the high amount of LacI binding at the lacO array leading to nucleosome eviction at this array and to the phosphorylation of H2A in the neighboring nucleosomes by Mec1 kinase. While the initial phosphorylation of H2A (H2A-P) and perinuclear anchoring are independent of the SIR complex, its latter recruitment stabilizes H2A-P and reinforces the perinuclear anchoring. Finally, we showed that Sir3 spreading stabilizes nucleosomes and limits the access of specific DNA-binding protein to DNA. Full article
(This article belongs to the Special Issue Regulation of Nuclear Organization and Function)
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22 pages, 5444 KiB  
Article
Zonula occludens 2 and Cell-Cell Contacts Are Required for Normal Nuclear Shape in Epithelia
Cells 2021, 10(10), 2568; https://doi.org/10.3390/cells10102568 - 28 Sep 2021
Cited by 3 | Viewed by 2441
Abstract
MAGUK protein ZO-2 is present at tight junctions (TJs) and nuclei. In MDCK ZO-2 knockdown (KD) cells, nuclei exhibit an irregular shape with lobules and indentations. This condition correlates with an increase in DNA double strand breaks, however cells are not senescent and [...] Read more.
MAGUK protein ZO-2 is present at tight junctions (TJs) and nuclei. In MDCK ZO-2 knockdown (KD) cells, nuclei exhibit an irregular shape with lobules and indentations. This condition correlates with an increase in DNA double strand breaks, however cells are not senescent and instead become resistant to UV-induced senescence. The irregular nuclear shape is also observed in isolated cells and in those without TJs, due to the lack of extracellular calcium. The aberrant nuclear shape of ZO-2 KD cells is not accompanied by a reduced expression of lamins A/C and B and lamin B receptors. Instead, it involves a decrease in constitutive and facultative heterochromatin, and microtubule instability that is restored with docetaxel. ZO-2 KD cells over-express SUN-1 that crosses the inner nuclear membrane and connects the nucleoskeleton of lamin A to nesprins, which traverse the outer nuclear membrane. Nesprins-3 and -4 that indirectly bind on their cytoplasmic face to vimentin and microtubules, respectively, are also over-expressed in ZO-2 KD cells, whereas vimentin is depleted. SUN-1 and lamin B1 co-immunoprecipitate with ZO-2, and SUN-1 associates to ZO-2 in a pull-down assay. Our results suggest that ZO-2 forms a complex with SUN-1 and lamin B1 at the inner nuclear membrane, and that ZO-2 and cell–cell contacts are required for a normal nuclear shape. Full article
(This article belongs to the Special Issue Regulation of Nuclear Organization and Function)
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25 pages, 3470 KiB  
Article
ChroMo, an Application for Unsupervised Analysis of Chromosome Movements in Meiosis
Cells 2021, 10(8), 2013; https://doi.org/10.3390/cells10082013 - 06 Aug 2021
Cited by 1 | Viewed by 2692
Abstract
Nuclear movements during meiotic prophase, driven by cytoskeleton forces, are a broadly conserved mechanism in opisthokonts and plants to promote pairing between homologous chromosomes. These forces are transmitted to the chromosomes by specific associations between telomeres and the nuclear envelope during meiotic prophase. [...] Read more.
Nuclear movements during meiotic prophase, driven by cytoskeleton forces, are a broadly conserved mechanism in opisthokonts and plants to promote pairing between homologous chromosomes. These forces are transmitted to the chromosomes by specific associations between telomeres and the nuclear envelope during meiotic prophase. Defective chromosome movements (CMs) harm pairing and recombination dynamics between homologues, thereby affecting faithful gametogenesis. For this reason, modelling the behaviour of CMs and their possible microvariations as a result of mutations or physico-chemical stress is important to understand this crucial stage of meiosis. Current developments in high-throughput imaging and image processing are yielding large CM datasets that are suitable for data mining approaches. To facilitate adoption of data mining pipelines, we present ChroMo, an interactive, unsupervised cloud application specifically designed for exploring CM datasets from live imaging. ChroMo contains a wide selection of algorithms and visualizations for time-series segmentation, motif discovery, and assessment of causality networks. Using ChroMo to analyse meiotic CMs in fission yeast, we found previously undiscovered features of CMs and causality relationships between chromosome morphology and trajectory. ChroMo will be a useful tool for understanding the behaviour of meiotic CMs in yeast and other model organisms. Full article
(This article belongs to the Special Issue Regulation of Nuclear Organization and Function)
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20 pages, 3812 KiB  
Article
New Data on Organization and Spatial Localization of B-Chromosomes in Cell Nuclei of the Yellow-Necked Mouse Apodemus flavicollis
Cells 2021, 10(7), 1819; https://doi.org/10.3390/cells10071819 - 19 Jul 2021
Cited by 2 | Viewed by 2690
Abstract
The gene composition, function and evolution of B-chromosomes (Bs) have been actively discussed in recent years. However, the additional genomic elements are still enigmatic. One of Bs mysteries is their spatial organization in the interphase nucleus. It is known that heterochromatic compartments are [...] Read more.
The gene composition, function and evolution of B-chromosomes (Bs) have been actively discussed in recent years. However, the additional genomic elements are still enigmatic. One of Bs mysteries is their spatial organization in the interphase nucleus. It is known that heterochromatic compartments are not randomly localized in a nucleus. The purpose of this work was to study the organization and three-dimensional spatial arrangement of Bs in the interphase nucleus. Using microdissection of Bs and autosome centromeric heterochromatic regions of the yellow-necked mouse (Apodemus flavicollis) we obtained DNA probes for further two-dimensional (2D)- and three-dimensional (3D)- fluorescence in situ hybridization (FISH) studies. Simultaneous in situ hybridization of obtained here B-specific DNA probes and autosomal C-positive pericentromeric region-specific probes further corroborated the previously stated hypothesis about the pseudoautosomal origin of the additional chromosomes of this species. Analysis of the spatial organization of the Bs demonstrated the peripheral location of B-specific chromatin within the interphase nucleus and feasible contact with the nuclear envelope (similarly to pericentromeric regions of autosomes and sex chromosomes). It is assumed that such interaction is essential for the regulation of nuclear architecture. It also points out that Bs may follow the same mechanism as sex chromosomes to avoid a meiotic checkpoint. Full article
(This article belongs to the Special Issue Regulation of Nuclear Organization and Function)
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Review

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19 pages, 1811 KiB  
Review
Chromosome Territories in Hematological Malignancies
Cells 2022, 11(8), 1368; https://doi.org/10.3390/cells11081368 - 17 Apr 2022
Cited by 2 | Viewed by 2647
Abstract
Chromosomes are organized in distinct nuclear areas designated as chromosome territories (CT). The structural formation of CT is a consequence of chromatin packaging and organization that ultimately affects cell function. Chromosome positioning can identify structural signatures of genomic organization, especially for diseases where [...] Read more.
Chromosomes are organized in distinct nuclear areas designated as chromosome territories (CT). The structural formation of CT is a consequence of chromatin packaging and organization that ultimately affects cell function. Chromosome positioning can identify structural signatures of genomic organization, especially for diseases where changes in gene expression contribute to a given phenotype. The study of CT in hematological diseases revealed chromosome position as an important factor for specific chromosome translocations. In this review, we highlight the history of CT theory, current knowledge on possible clinical applications of CT analysis, and the impact of CT in the development of hematological neoplasia such as multiple myeloma, leukemia, and lymphomas. Accumulating data on nuclear architecture in cancer allow one to propose the three-dimensional nuclear genomic landscape as a novel cancer biomarker for the future. Full article
(This article belongs to the Special Issue Regulation of Nuclear Organization and Function)
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22 pages, 1282 KiB  
Review
Chromatin Organization and Function in Drosophila
Cells 2021, 10(9), 2362; https://doi.org/10.3390/cells10092362 - 08 Sep 2021
Cited by 6 | Viewed by 4315
Abstract
Eukaryotic genomes are packaged into high-order chromatin structures organized in discrete territories inside the cell nucleus, which is surrounded by the nuclear envelope acting as a barrier. This chromatin organization is complex and dynamic and, thus, determining the spatial and temporal distribution and [...] Read more.
Eukaryotic genomes are packaged into high-order chromatin structures organized in discrete territories inside the cell nucleus, which is surrounded by the nuclear envelope acting as a barrier. This chromatin organization is complex and dynamic and, thus, determining the spatial and temporal distribution and folding of chromosomes within the nucleus is critical for understanding the role of chromatin topology in genome function. Primarily focusing on the regulation of gene expression, we review here how the genome of Drosophila melanogaster is organized into the cell nucleus, from small scale histone–DNA interactions to chromosome and lamina interactions in the nuclear space. Full article
(This article belongs to the Special Issue Regulation of Nuclear Organization and Function)
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