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Chromatin Architecture: A Flexible Foundation for Gene Expression
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Chromatin Architecture: A Flexible Foundation for Gene Expression

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

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 11939

Special Issue Editor

Dr. Igor Kireev

E-Mail Website
Guest Editor
Department of Electron Microscopy, Andrey N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1-40 Leninskie Gory, 119234 Moscow, Russia
Interests: chromatin higher order organization; chromatin–nuclear envelope interactions; SMC proteins in chromatin dynamics

Special Issue Information

Dear Colleagues,

In eukaryotic cells, DNA is organized into highly structured chromatin that serves as a template for multiple genetic functions (transcription, replication repair, etc.). The differential structural organization of chromatin observed at various levels—from nucleosomes to chromatin domains to chromosomal territories—is highly dynamic, not simply reflecting the adaptation of the local chromatin structure to the needs of gene expression but rather a regulatory act controlling the efficiency of genetic processes. As a consequence, chromatin organization per se can be considered an epigenetic factor along with histone modifications, DNA methylation, and regulatory RNAs. The complexity and multi-scale nature of chromatin organization requires a complex approach that includes the characterization of its molecular components and correlative studies of its spatial arrangement performed on a multitude of finely tuned gene loci with characteristic non-uniform chromatin folding. In this Special Issue, "Chromatin Architecture: A Flexible Foundation for Gene Expression", we invite papers on different aspects of chromatin plasticity related to gene activity, studied at multiple scales from molecular events up to nuclear 3D-architecture, and the mechanisms underlying the structural rearrangement of chromatin. We also welcome contributions that concern recent technical advances in studies of chromatin organization and dynamics at various levels, including, but not limited to, molecular and genomic approaches and imaging techniques.

Dr. Igor Kireev
Guest Editor

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Keywords

  • chromatin
  • epigenetics
  • transcription
  • chromatin domains
  • nuclear 3D-architecture

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Published Papers (4 papers)

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Review

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16 pages, 10785 KiB  
Review
Involvement of the H3.3 Histone Variant in the Epigenetic Regulation of Gene Expression in the Nervous System, in Both Physiological and Pathological Conditions
by Carlo Maria Di Liegro, Gabriella Schiera, Giuseppe Schirò and Italia Di Liegro
Int. J. Mol. Sci. 2023, 24(13), 11028; https://doi.org/10.3390/ijms241311028 - 3 Jul 2023
Cited by 3 | Viewed by 1967
Abstract
All the cells of an organism contain the same genome. However, each cell expresses only a minor fraction of its potential and, in particular, the genes encoding the proteins necessary for basal metabolism and the proteins responsible for its specific phenotype. The ability [...] Read more.
All the cells of an organism contain the same genome. However, each cell expresses only a minor fraction of its potential and, in particular, the genes encoding the proteins necessary for basal metabolism and the proteins responsible for its specific phenotype. The ability to use only the right and necessary genes involved in specific functions depends on the structural organization of the nuclear chromatin, which in turn depends on the epigenetic history of each cell, which is stored in the form of a collection of DNA and protein modifications. Among these modifications, DNA methylation and many kinds of post-translational modifications of histones play a key role in organizing the complex indexing of usable genes. In addition, non-canonical histone proteins (also known as histone variants), the synthesis of which is not directly linked with DNA replication, are used to mark specific regions of the genome. Here, we will discuss the role of the H3.3 histone variant, with particular attention to its loading into chromatin in the mammalian nervous system, both in physiological and pathological conditions. Indeed, chromatin modifications that mark cell memory seem to be of special importance for the cells involved in the complex processes of learning and memory. Full article
(This article belongs to the Special Issue Chromatin Architecture: A Flexible Foundation for Gene Expression)
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19 pages, 3167 KiB  
Review
Unveiling the Machinery behind Chromosome Folding by Polymer Physics Modeling
by Mattia Conte, Andrea Esposito, Francesca Vercellone, Alex Abraham and Simona Bianco
Int. J. Mol. Sci. 2023, 24(4), 3660; https://doi.org/10.3390/ijms24043660 - 11 Feb 2023
Cited by 3 | Viewed by 2547
Abstract
Understanding the mechanisms underlying the complex 3D architecture of mammalian genomes poses, at a more fundamental level, the problem of how two or multiple genomic sites can establish physical contacts in the nucleus of the cells. Beyond stochastic and fleeting encounters related to [...] Read more.
Understanding the mechanisms underlying the complex 3D architecture of mammalian genomes poses, at a more fundamental level, the problem of how two or multiple genomic sites can establish physical contacts in the nucleus of the cells. Beyond stochastic and fleeting encounters related to the polymeric nature of chromatin, experiments have revealed specific, privileged patterns of interactions that suggest the existence of basic organizing principles of folding. In this review, we focus on two major and recently proposed physical processes of chromatin organization: loop-extrusion and polymer phase-separation, both supported by increasing experimental evidence. We discuss their implementation into polymer physics models, which we test against available single-cell super-resolution imaging data, showing that both mechanisms can cooperate to shape chromatin structure at the single-molecule level. Next, by exploiting the comprehension of the underlying molecular mechanisms, we illustrate how such polymer models can be used as powerful tools to make predictions in silico that can complement experiments in understanding genome folding. To this aim, we focus on recent key applications, such as the prediction of chromatin structure rearrangements upon disease-associated mutations and the identification of the putative chromatin organizing factors that orchestrate the specificity of DNA regulatory contacts genome-wide. Full article
(This article belongs to the Special Issue Chromatin Architecture: A Flexible Foundation for Gene Expression)
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31 pages, 1365 KiB  
Review
Targeting Chromatin-Remodeling Factors in Cancer Cells: Promising Molecules in Cancer Therapy
by Fang-Lin Zhang and Da-Qiang Li
Int. J. Mol. Sci. 2022, 23(21), 12815; https://doi.org/10.3390/ijms232112815 - 24 Oct 2022
Cited by 16 | Viewed by 5429
Abstract
ATP-dependent chromatin-remodeling complexes can reorganize and remodel chromatin and thereby act as important regulator in various cellular processes. Based on considerable studies over the past two decades, it has been confirmed that the abnormal function of chromatin remodeling plays a pivotal role in [...] Read more.
ATP-dependent chromatin-remodeling complexes can reorganize and remodel chromatin and thereby act as important regulator in various cellular processes. Based on considerable studies over the past two decades, it has been confirmed that the abnormal function of chromatin remodeling plays a pivotal role in genome reprogramming for oncogenesis in cancer development and/or resistance to cancer therapy. Recently, exciting progress has been made in the identification of genetic alteration in the genes encoding the chromatin-remodeling complexes associated with tumorigenesis, as well as in our understanding of chromatin-remodeling mechanisms in cancer biology. Here, we present preclinical evidence explaining the signaling mechanisms involving the chromatin-remodeling misregulation-induced cancer cellular processes, including DNA damage signaling, metastasis, angiogenesis, immune signaling, etc. However, even though the cumulative evidence in this field provides promising emerging molecules for therapeutic explorations in cancer, more research is needed to assess the clinical roles of these genetic cancer targets. Full article
(This article belongs to the Special Issue Chromatin Architecture: A Flexible Foundation for Gene Expression)
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Other

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12 pages, 1889 KiB  
Perspective
Unnatural Amino Acid Crosslinking for Increased Spatiotemporal Resolution of Chromatin Dynamics
by Pamela Moleri and Bryan J. Wilkins
Int. J. Mol. Sci. 2023, 24(16), 12879; https://doi.org/10.3390/ijms241612879 - 17 Aug 2023
Viewed by 1280
Abstract
The utilization of an expanded genetic code and in vivo unnatural amino acid crosslinking has grown significantly in the past decade, proving to be a reliable system for the examination of protein–protein interactions. Perhaps the most utilized amino acid crosslinker, p-benzoyl-(l [...] Read more.
The utilization of an expanded genetic code and in vivo unnatural amino acid crosslinking has grown significantly in the past decade, proving to be a reliable system for the examination of protein–protein interactions. Perhaps the most utilized amino acid crosslinker, p-benzoyl-(l)-phenylalanine (pBPA), has delivered a vast compendium of structural and mechanistic data, placing it firmly in the upper echelons of protein analytical techniques. pBPA contains a benzophenone group that is activated with low energy radiation (~365 nm), initiating a diradical state that can lead to hydrogen abstraction and radical recombination in the form of a covalent bond to a neighboring protein. Importantly, the expanded genetic code system provides for site-specific encoding of the crosslinker, yielding spatial control for protein surface mapping capabilities. Paired with UV-activation, this process offers a practical means for spatiotemporal understanding of protein–protein dynamics in the living cell. The chromatin field has benefitted particularly well from this technique, providing detailed mapping and mechanistic insight for numerous chromatin-related pathways. We provide here a brief history of unnatural amino acid crosslinking in chromatin studies and outlooks into future applications of the system for increased spatiotemporal resolution in chromatin related research. Full article
(This article belongs to the Special Issue Chromatin Architecture: A Flexible Foundation for Gene Expression)
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