Dynamic chromatin organization in the cell

2019 ◽  
Vol 63 (1) ◽  
pp. 133-145 ◽  
Author(s):  
Eloise I. Prieto ◽  
Kazuhiro Maeshima

Abstract The organization and regulation of genomic DNA as nuclear chromatin is necessary for proper DNA function inside living eukaryotic cells. While this has been extensively explored, no true consensus is currently reached regarding the exact mechanism of chromatin organization. The traditional view has assumed that the DNA is packaged into a hierarchy of structures inside the nucleus based on the regular 30-nm chromatin fiber. This is currently being challenged by the fluid-like model of the chromatin which views the chromatin as a dynamic structure based on the irregular 10-nm fiber. In this review, we focus on the recent progress in chromatin structure elucidation highlighting the paradigm shift in chromatin folding mechanism from the classical textbook perspective of the regularly folded chromatin to the more dynamic fluid-like perspective.

Author(s):  
W.W. Franke ◽  
H. Zentgraf ◽  
U. Scheer

A significant contribution to the understanding of chromatin organization was the discovery of the nucleosome as a globular repeating unit of the package of DNA (Hewish and Burgoyne, 1973; Woodcock, 1973; Kornberg, 1974; Olins and Olins, 1974; for review see Oudet et al., 1978a). In accord with the original definition and in agreement with most workers in this field of research we identify a nucleosome as a spherical or slightly oblate granular particle 10-13 nm in diameter, containing about 200 base pairs of DNA and two of each of the four histones H2a, H2b, H3 and H4. It is this structure in which the bulk of the nuclear chromatin is organized in most eukaryotic cells, with the exception of the dinoflagellates (Rae and Steele, 1977; dinoflagellate DNA, however, can be packed into nucleosomal structures in vitro by addition of the appropriate amounts of histones;the same reference).


2018 ◽  
Vol 47 (19) ◽  
pp. 6654-6659 ◽  
Author(s):  
Michael Schmittel

This personal frontier account describes our recent progress in networking nanoswitches to generate emergent functions, such as catalytic machinery, and identifies the key impediments in mastering the paradigm shift from pure compounds to smart mixtures.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2764
Author(s):  
Agustina P. Bertolin ◽  
Jean-Sébastien Hoffmann ◽  
Vanesa Gottifredi

In this review, we provide an overview of how proliferating eukaryotic cells overcome one of the main threats to genome stability: incomplete genomic DNA replication during S phase. We discuss why it is currently accepted that double fork stalling (DFS) events are unavoidable events in higher eukaryotes with large genomes and which responses have evolved to cope with its main consequence: the presence of under-replicated DNA (UR-DNA) outside S phase. Particular emphasis is placed on the processes that constrain the detrimental effects of UR-DNA. We discuss how mitotic DNA synthesis (MiDAS), mitotic end joining events and 53BP1 nuclear bodies (53BP1-NBs) deal with such specific S phase DNA replication remnants during the subsequent phases of the cell cycle.


2014 ◽  
Vol 42 (15) ◽  
pp. 9553-9561 ◽  
Author(s):  
Daniel Jost ◽  
Pascal Carrivain ◽  
Giacomo Cavalli ◽  
Cédric Vaillant

Abstract Genomes of eukaryotes are partitioned into domains of functionally distinct chromatin states. These domains are stably inherited across many cell generations and can be remodeled in response to developmental and external cues, hence contributing to the robustness and plasticity of expression patterns and cell phenotypes. Remarkably, recent studies indicate that these 1D epigenomic domains tend to fold into 3D topologically associated domains forming specialized nuclear chromatin compartments. However, the general mechanisms behind such compartmentalization including the contribution of epigenetic regulation remain unclear. Here, we address the question of the coupling between chromatin folding and epigenome. Using polymer physics, we analyze the properties of a block copolymer model that accounts for local epigenomic information. Considering copolymers build from the epigenomic landscape of Drosophila, we observe a very good agreement with the folding patterns observed in chromosome conformation capture experiments. Moreover, this model provides a physical basis for the existence of multistability in epigenome folding at sub-chromosomal scale. We show how experiments are fully consistent with multistable conformations where topologically associated domains of the same epigenomic state interact dynamically with each other. Our approach provides a general framework to improve our understanding of chromatin folding during cell cycle and differentiation and its relation to epigenetics.


2019 ◽  
Author(s):  
Miao Liu ◽  
Yanfang Lu ◽  
Bing Yang ◽  
Yanbo Chen ◽  
Jonathan S.D. Radda ◽  
...  

AbstractThe three-dimensional architecture of the genome affects genomic functions. Multiple genome architectures at different length scales, including chromatin loops, domains, compartments, and regions associated with nuclear lamina and nucleoli, have been discovered. However, how these structures are arranged in the same cell and how they are correlated with each other in different cell types in mammalian tissue are largely unknown. Here, we developed Multiplexed Imaging of Nucleome Architectures that measures multiscale chromatin folding, copy numbers of numerous RNA species, and associations of numerous genomic regions with nuclear lamina, nucleoli and surface of chromosomes in the same, single cells. We applied this method in mouse fetal liver, and identified de novo cell-type-specific chromatin architectures associated with gene expression, as well as chromatin organization principles independent of cell type. Polymer simulation showed that both intra-chromosomal phase-separating interactions and extra-chromosomal interactions are necessary to establish the observed organization. Our experiments and modeling provide a multiscale and multi-faceted picture of chromatin folding and nucleome architectures in mammalian tissue and illustrate physical principles for maintaining chromatin organization.


2020 ◽  
Vol 12 (22) ◽  
pp. 2795-2811 ◽  
Author(s):  
Houman Kholafazad Kordasht ◽  
Mohammad Hasanzadeh

Exosomes are membrane-bound extracellular vesicles (EVs) that are produced in the endosomal compartments of most eukaryotic cells; they play important roles in intercellular communication in diverse cellular processes and transmit different types of biomolecules.


2015 ◽  
Vol 370 (1678) ◽  
pp. 20140318 ◽  
Author(s):  
Tom A. Williams ◽  
T. Martin Embley

The origin of eukaryotic cells is one of the most fascinating challenges in biology, and has inspired decades of controversy and debate. Recent work has led to major upheavals in our understanding of eukaryotic origins and has catalysed new debates about the roles of endosymbiosis and gene flow across the tree of life. Improved methods of phylogenetic analysis support scenarios in which the host cell for the mitochondrial endosymbiont was a member of the Archaea, and new technologies for sampling the genomes of environmental prokaryotes have allowed investigators to home in on closer relatives of founding symbiotic partners. The inference and interpretation of phylogenetic trees from genomic data remains at the centre of many of these debates, and there is increasing recognition that trees built using inadequate methods can prove misleading, whether describing the relationship of eukaryotes to other cells or the root of the universal tree. New statistical approaches show promise for addressing these questions but they come with their own computational challenges. The papers in this theme issue discuss recent progress on the origin of eukaryotic cells and genomes, highlight some of the ongoing debates, and suggest possible routes to future progress.


Author(s):  
Keishi Osakabe ◽  
Naoki Wada ◽  
Emi Murakami ◽  
Yuriko Osakabe

SUMMARYAdoption of the CRISPR-Cas system has revolutionized genome engineering in recent years; however, application of genome editing with CRISPR type I—the most abundant CRISPR system in bacteria—has been less developed. Type I systems in which Cas3 nuclease degrades the target DNA are known; in contrast, for the sub-type CRISPR type I-D (TiD), which lacks a typical Cas3 nuclease in its cascade, the mechanism of target DNA degradation remains unknown. Here, we found that Cas10d—a nuclease in TiD—is multi-functional in PAM recognition, stabilization and target DNA degradation. TiD can be used for targeted mutagenesis of genomic DNA in human cells, directing both bi-directional long-range deletions and short insertions/deletions. TiD off-target effects, which were dependent on the mismatch position in the protospacer of TiD, were also identified. Our findings suggest TiD as a unique effector pathway in CRISPR that can be repurposed for genome engineering in eukaryotic cells.


2021 ◽  
Vol 9 (S1-May) ◽  
pp. 154-161
Author(s):  
Ahmet Selçuk Akdemir

Willingness to communicate (WTC), a recent affective construct of SLA research, has experienced a paradigm shift regarding its nature. Current WTC research tends to define it as a dynamic and context-bound structure rather being in a linear and static disposition. New conceptualization is based on Complex Dynamic System (CDS) theory. This theory has been applied to SLA research to explain dynamic, non-linear and complex nature of SLA process. The convenience of CDS theory’s basic principles has led existing WTC structure to be re-shaped and revised to define it as a dynamic structure in contrast to its former definition which would recall WTC as a static and trait-like variable.


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