This article analyzes the results of the 2022 US midterm elections and looks ahead to the trends in US political diplomacy after the elections. Results from the midterm elections were more successful ...than expected for the Democratic Party, and there appears to be a tailwind for the Joe Biden administration. However, the international situation remains difficult to navigate due to the ongoing divisions in the US, the situation in Ukraine, and tensions in the Taiwan Strait. It then discusses how Japan should respond to the worsening security environment after the elections, including some long-term perspectives. Japan and the US need to transform the mindset from mere alliance maintenance of the past to develop ways to fully utilize the alliance (alliance projection), and to cooperate in preventing moves to change the status quo in the Indo-Pacific region. The Kishida Fumio administration issued three revised security documents, including the National Security Strategy, in December 2022, and Japan is now moving toward having not only a "shield" but also a "spear." In order to deepen the Japan-US alliance and to work with the Indo-Pacific nations, it is essential to gain strong support from the public.
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Chromatin in eukaryotic cells is a negatively charged polymer composed of DNA, histones, and various associated proteins. Over the past ten years, our view of chromatin has shifted from a static ...regular structure to a dynamic and highly variable configuration. While the details are not fully understood yet, chromatin forms numerous compact domains that act as dynamic functional units of the genome in higher eukaryotes. By altering DNA accessibility, the dynamic nature of chromatin governs various genome functions including RNA transcription, DNA replication, and DNA repair/recombination. Based on the new evidence coming from both genomics and imaging studies, we discuss the structural and dynamic aspects of chromatin and their biological relevance in the living cell.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei ...must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We address this by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin. We find that the mechanical rigidity of nuclei depends on the continuity of the nucleosomal fiber and interactions between nucleosomes. Disrupting these chromatin features by varying cation concentration, acetylating histone tails, or digesting linker DNA results in loss of nuclear rigidity. In contrast, the levels of key chromatin assembly factors, including cohesin, condensin II, and CTCF, and a major nuclear envelope protein, lamin, are unaffected. Together with in situ evidence using living cells and a simple mechanical model, our findings reveal a chromatin-based regulation of the nuclear mechanical response and provide insight into the significance of local and global chromatin structures, such as those associated with interdigitated or melted nucleosomal fibers.
The mammalian genome is organized into submegabase-sized chromatin domains (CDs) including topologically associating domains, which have been identified using chromosome conformation capture-based ...methods. Single-nucleosome imaging in living mammalian cells has revealed subdiffusively dynamic nucleosome movement. It is unclear how single nucleosomes within CDs fluctuate and how the CD structure reflects the nucleosome movement. Here, we present a polymer model wherein CDs are characterized by fractal dimensions and the nucleosome fibers fluctuate in a viscoelastic medium with memory. We analytically show that the mean-squared displacement (MSD) of nucleosome fluctuations within CDs is subdiffusive. The diffusion coefficient and the subdiffusive exponent depend on the structural information of CDs. This analytical result enabled us to extract information from the single-nucleosome imaging data for HeLa cells. Our observation that the MSD is lower at the nuclear periphery region than the interior region indicates that CDs in the heterochromatin-rich nuclear periphery region are more compact than those in the euchromatin-rich interior region with respect to the fractal dimensions as well as the size. Finally, we evaluated that the average size of CDs is in the range of 100-500 nm and that the relaxation time of nucleosome movement within CDs is a few seconds. Our results provide physical and dynamic insights into the genome architecture in living cells.
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Physical Nature of Chromatin in the Nucleus Maeshima, Kazuhiro; Iida, Shiori; Tamura, Sachiko
Cold Spring Harbor perspectives in biology,
05/2021, Volume:
13, Issue:
5
Journal Article
Peer reviewed
Open access
Genomic information is encoded on long strands of DNA, which are folded into chromatin and stored in a tiny nucleus. Nuclear chromatin is a negatively charged polymer composed of DNA, histones, and ...various nonhistone proteins. Because of its highly charged nature, chromatin structure varies greatly depending on the surrounding environment (e.g., cations, molecular crowding, etc.). New technologies to capture chromatin in living cells have been developed over the past 10 years. Our view on chromatin organization has drastically shifted from a regular and static one to a more variable and dynamic one. Chromatin forms numerous compact dynamic domains that act as functional units of the genome in higher eukaryotic cells and locally appear liquid-like. By changing DNA accessibility, these domains can govern various functions. Based on new evidences from versatile genomics and advanced imaging studies, we discuss the physical nature of chromatin in the crowded nuclear environment and how it is regulated.
Eukaryotic genome DNA is wrapped around core histones and forms a nucleosome structure. Together with associated proteins and RNAs, these nucleosomes are organized three‐dimensionally in the cell as ...chromatin. Emerging evidence demonstrates that chromatin consists of rather irregular and variable nucleosome arrangements without the regular fiber structure and that its dynamic behavior plays a critical role in regulating various genome functions. Single‐nucleosome imaging is a promising method to investigate chromatin behavior in living cells. It reveals local chromatin motion, which reflects chromatin organization not observed in chemically fixed cells. The motion data is like a gold mine. Data analyses from many aspects bring us more and more information that contributes to better understanding of genome functions. In this review article, we describe imaging of single‐nucleosomes and their tracked behavior through oblique illumination microscopy. We also discuss applications of this technique, especially in elucidating nucleolar organization in living cells.
Single‐nucleosome imaging and tracking is a promising technique to investigate dynamic chromatin behavior in living cells. We describe how this imaging works using sparse nucleosome labeling and oblique illumination microscopy, and how information on chromatin dynamics can be extracted from the obtained motion data.
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The eukaryotic genome is organized within cells as chromatin. For proper information output, higher-order chromatin structures can be regulated dynamically. How such structures form and behave in ...various cellular processes remains unclear. Here, by combining super-resolution imaging (photoactivated localization microscopy PALM) and single-nucleosome tracking, we developed a nuclear imaging system to visualize the higher-order structures along with their dynamics in live mammalian cells. We demonstrated that nucleosomes form compact domains with a peak diameter of ∼160 nm and move coherently in live cells. The heterochromatin-rich regions showed more domains and less movement. With cell differentiation, the domains became more apparent, with reduced dynamics. Furthermore, various perturbation experiments indicated that they are organized by a combination of factors, including cohesin and nucleosome-nucleosome interactions. Notably, we observed the domains during mitosis, suggesting that they act as building blocks of chromosomes and may serve as information units throughout the cell cycle.
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•We visualized chromatin structures and their dynamics in live mammalian cells•Nucleosomes form compact chromatin domains in live cells and move coherently•The domains are organized by nucleosome-nucleosome interactions and cohesin•The domains exist during mitosis and act as building blocks of chromosomes
How a genome is organized and behaves in live cells remains unclear. Nozaki et al. visualized little bunches of chromatin, “chromatin domains,” and their dynamic behavior in live mammalian cells. The domains can work as “Lego blocks” of chromosomes to maintain genetic information throughout the cell cycle.
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Understanding chromatin organization and dynamics is important, since they crucially affect DNA functions. In this study, we investigate chromatin dynamics by statistically analyzing ...single-nucleosome movement in living human cells. Bimodal nature of the mean square displacement distribution of nucleosomes allows for a natural categorization of the nucleosomes as fast and slow. Analyses of the nucleosome–nucleosome correlation functions within these categories along with the density of vibrational modes show that the nucleosomes form dynamically correlated fluid regions (i.e., dynamic domains of fast and slow nucleosomes). Perturbed nucleosome dynamics by global histone acetylation or cohesin inactivation indicate that nucleosome–nucleosome interactions along with tethering of chromatin chains organize nucleosomes into fast and slow dynamic domains. A simple polymer model is introduced, which shows the consistency of this dynamic domain picture. Statistical analyses of single-nucleosome movement provide rich information on how chromatin is dynamically organized in a fluid manner in living cells.
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