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Chromatin Organization during Cell Differentiation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 14154

Special Issue Editors


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Guest Editor
Department Biological, Geological and Environmental Sciences, University of Catania, 95124 Catania, Italy
Interests: genetics; genomics; molecular cytogenetics; chromosomes; nuclear chromatin organization; evolutionary genetics; developmental genetics; forensic genetics; environmental mutagenesis; epigenetics
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Biological, Geological and Environmental Sciences, University of Catania, 95124 Catania, Italy
Interests: chromosome organization and evolution; DNA polymorphisms in forensic genetics; neurodegeneration; human genetic diseases; environmental mutagenesis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Life Sciences, Brunel University London, Progeria Research Team, Uxbridge UB8 3PH, UK
Interests: Genome organisation; Nuclear motors; Cellular and Organismal Ageing; Host:pathogen interactions; Stem cell Genomic Health; Premature ageing; Nuclear structures

Special Issue Information

Dear Colleagues,

Recent studies have highlighted the relevance of the chromosome organization in the cell nucleus for the correct expression of the genes. The two main chromatin compartments, A and B, identified by HiC analyses, are endowed with very different structural and functional properties: the former is very gene-dense and is replicated early on, mainly located in the inner part of the nucleus, and the other is gene-poor and is replicated late, located at the nuclear and the nucleolar periphery. This organization is highly dynamic, allowing a repositioning of genes and chromosomes within nuclei during cell differentiation to correctly reorganize expressing genes. Disturbances in chromatin organization during cell differentiation could be responsible for future genome malfunction, subsequently leading to genetic diseases.

In this Special Issue, we aim to publish reviews and original papers covering recent advances in the dynamic reorganization of genes, chromatin and chromosomes within cell nuclei, not only during normal cell differentiation but also in pathological conditions, and we invite colleagues to present papers in this topic.

Prof. Dr. Salvatore Saccone
Dr. Concetta Federico
Prof. Dr. Joanna Bridger
Guest Editors

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Keywords

  • cell nucleus
  • nucleolar activity
  • Topologically Associated Domains (TADs)
  • cell differentiation
  • CTCF protein
  • insulators
  • chromatin architecture
  • chromosome evolution
  • HiC: FISH

Published Papers (4 papers)

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Research

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16 pages, 7791 KiB  
Article
From FISH to Hi-C: The Chromatin Architecture of the Chromosomal Region 7q36.3, Frequently Rearranged in Leukemic Cells, Is Evolutionary Conserved
by Gesualda M. Gulino, Francesca Bruno, Valentina Sturiale, Desiree Brancato, Denise Ragusa, Sabrina Tosi, Salvatore Saccone and Concetta Federico
Int. J. Mol. Sci. 2021, 22(5), 2338; https://doi.org/10.3390/ijms22052338 - 26 Feb 2021
Cited by 5 | Viewed by 2762
Abstract
Fluorescence in situ hybridization (FISH) and Hi-C methods are largely used to investigate the three-dimensional organization of the genome in the cell nucleus and are applied here to study the organization of genes (LMBR1, NOM1, MNX1, UBE3C, PTPRN2 [...] Read more.
Fluorescence in situ hybridization (FISH) and Hi-C methods are largely used to investigate the three-dimensional organization of the genome in the cell nucleus and are applied here to study the organization of genes (LMBR1, NOM1, MNX1, UBE3C, PTPRN2) localized in the human 7q36.3 band. This region contains the MNX1 gene, which is normally not expressed in human lymphocytes beyond embryonic development. However, this homeobox gene is frequently activated in leukemic cells and its expression is associated with an altered gene positioning in the leukemia cell nuclei. In this study, we used FISH on 3D-preserved nuclei to investigate the nuclear positioning of MNX1 in the leukemia-derived cell line K562. Of the five copies of the MNX1 gene present in K562, four alleles were positioned in the nuclear periphery and only one in the nuclear interior. Using the Juicebox’s Hi-C dataset, we identified five chromatin loops in the 7q36.3 band, with different extensions related to the size and orientation of the genes located here, and independent from their expression levels. We identified similar loops in 11 human and three mouse cell lines, showing that these loops are highly conserved in different human cell lines and during evolution. Moreover, the chromatin loop organization is well conserved also during neuronal cell differentiation, showing consistency in genomic organization of this region in development. In this report, we show that FISH and Hi-C are two different approaches that complement one another and together give complete information on the nuclear organization of specific chromosomal regions in different conditions, including cellular differentiation and genetic diseases. Full article
(This article belongs to the Special Issue Chromatin Organization during Cell Differentiation)
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Review

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12 pages, 994 KiB  
Review
Chromosomal Rearrangements and Chromothripsis: The Alternative End Generation Model
by Daniel de Groot, Aldo Spanjaard, Marc A. Hogenbirk and Heinz Jacobs
Int. J. Mol. Sci. 2023, 24(1), 794; https://doi.org/10.3390/ijms24010794 - 2 Jan 2023
Cited by 1 | Viewed by 2580
Abstract
Chromothripsis defines a genetic phenomenon where up to hundreds of clustered chromosomal rearrangements can arise in a single catastrophic event. The phenomenon is associated with cancer and congenital diseases. Most current models on the origin of chromothripsis suggest that prior to chromatin reshuffling [...] Read more.
Chromothripsis defines a genetic phenomenon where up to hundreds of clustered chromosomal rearrangements can arise in a single catastrophic event. The phenomenon is associated with cancer and congenital diseases. Most current models on the origin of chromothripsis suggest that prior to chromatin reshuffling numerous DNA double-strand breaks (DSBs) have to exist, i.e., chromosomal shattering precedes rearrangements. However, the preference of a DNA end to rearrange in a proximal accessible region led us to propose chromothripsis as the reaction product of successive chromatin rearrangements. We previously coined this process Alternative End Generation (AEG), where a single DSB with a repair-blocking end initiates a domino effect of rearrangements. Accordingly, chromothripsis is the end product of this domino reaction taking place in a single catastrophic event. Full article
(This article belongs to the Special Issue Chromatin Organization during Cell Differentiation)
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14 pages, 1163 KiB  
Review
Dosage Compensation in Drosophila: Its Canonical and Non-Canonical Mechanisms
by Yuri Y. Shevelyov, Sergey V. Ulianov, Mikhail S. Gelfand, Stepan N. Belyakin and Sergey V. Razin
Int. J. Mol. Sci. 2022, 23(18), 10976; https://doi.org/10.3390/ijms231810976 - 19 Sep 2022
Cited by 1 | Viewed by 3676
Abstract
Dosage compensation equalizes gene expression in a single male X chromosome with that in the pairs of autosomes and female X chromosomes. In the fruit fly Drosophila, canonical dosage compensation is implemented by the male-specific lethal (MSL) complex functioning in all male [...] Read more.
Dosage compensation equalizes gene expression in a single male X chromosome with that in the pairs of autosomes and female X chromosomes. In the fruit fly Drosophila, canonical dosage compensation is implemented by the male-specific lethal (MSL) complex functioning in all male somatic cells. This complex contains acetyl transferase males absent on the first (MOF), which performs H4K16 hyperacetylation specifically in the male X chromosome, thus facilitating transcription of the X-linked genes. However, accumulating evidence points to an existence of additional, non-canonical dosage compensation mechanisms operating in somatic and germline cells. In this review, we discuss current advances in the understanding of both canonical and non-canonical mechanisms of dosage compensation in Drosophila. Full article
(This article belongs to the Special Issue Chromatin Organization during Cell Differentiation)
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15 pages, 885 KiB  
Review
Phospho-Tau and Chromatin Landscapes in Early and Late Alzheimer’s Disease
by Laura Gil, Sandra A. Niño, Carmen Guerrero and María E. Jiménez-Capdeville
Int. J. Mol. Sci. 2021, 22(19), 10283; https://doi.org/10.3390/ijms221910283 - 24 Sep 2021
Cited by 6 | Viewed by 3982
Abstract
Cellular identity is determined through complex patterns of gene expression. Chromatin, the dynamic structure containing genetic information, is regulated through epigenetic modulators, mainly by the histone code. One of the main challenges for the cell is maintaining functionality and identity, despite the accumulation [...] Read more.
Cellular identity is determined through complex patterns of gene expression. Chromatin, the dynamic structure containing genetic information, is regulated through epigenetic modulators, mainly by the histone code. One of the main challenges for the cell is maintaining functionality and identity, despite the accumulation of DNA damage throughout the aging process. Replicative cells can remain in a senescent state or develop a malign cancer phenotype. In contrast, post-mitotic cells such as pyramidal neurons maintain extraordinary functionality despite advanced age, but they lose their identity. This review focuses on tau, a protein that protects DNA, organizes chromatin, and plays a crucial role in genomic stability. In contrast, tau cytosolic aggregates are considered hallmarks of Alzheimer´s disease (AD) and other neurodegenerative disorders called tauopathies. Here, we explain AD as a phenomenon of chromatin dysregulation directly involving the epigenetic histone code and a progressive destabilization of the tau–chromatin interaction, leading to the consequent dysregulation of gene expression. Although this destabilization could be lethal for post-mitotic neurons, tau protein mediates profound cellular transformations that allow for their temporal survival. Full article
(This article belongs to the Special Issue Chromatin Organization during Cell Differentiation)
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