Kazuhiro Maeshima

Kazuhiro Maeshima
National Institute of Genetics · Structural Biology Center

PhD

About

118
Publications
25,090
Reads
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5,880
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Introduction
Our research interest is to know how a long string of genomic DNA is three-dimensionally organized in the mammalian cells, and how the organized genome functions during cellular proliferation, differentiation, and development. We are using a novel combination of molecular cell biology and biophysics to elucidate 3D-organization and dynamics of genome DNA. Positions for motivated students and postdocs are available: http://maeshima-lab.sakuraweb.com/positions.html
Additional affiliations
April 2009 - present
National Institute of Genetics
Position
  • Professor (Full)
April 2009 - present
SOKENDAI (The Graduate University for Advanced Studies)
Position
  • Professor
June 2004 - March 2009
RIKEN
Position
  • Research Scientist

Publications

Publications (118)
Article
Full-text available
The existence of a 30-nm fiber as a basic folding unit for DNA packaging has remained a topic of active discussion. Here, we characterize the supramolecular structures formed by reversible Mg(2+)-dependent self-association of linear 12-mer nucleosomal arrays using microscopy and physicochemical approaches. These reconstituted chromatin structures,...
Article
Full-text available
Eukaryotic chromatin is a negatively charged long polymer composed of genomic DNA, histones, and various proteins. The charged property causes the chromatin structure to be dynamically changed. These dynamic changes are critical for genome functions such as gene expression because they directly govern the degree of DNA accessibility. Although the c...
Article
Full-text available
Chromatin DNA must be read out for various cellular functions, and copied for the next cell division. These processes are targets of many anticancer agents. Platinum-based drugs, such as cisplatin, have been used extensively in cancer chemotherapy. The drug–DNA interaction causes DNA crosslinks and subsequent cytotoxicity. Recently, it was reported...
Article
Full-text available
Pyrrole-Imidazole (PI) polyamides bind to specific DNA sequences in the minor groove with high affinity. Specific DNA labeling by PI polyamides does not require DNA denaturation with harsh treatments of heat and formamide and has the advantages of rapid and less disruptive processing. Previously, we developed tandem hairpin PI polyamide probes (TH5...
Article
Full-text available
Chromatin organization has an important role in the regulation of eukaryotic systems. While recent studies have refined the 3-D models of chromatin organization with high resolution at the genome sequence level, little is known about how the most fundamental units of chromatin - nucleosomes - are positioned in 3-D in vivo Here we have used electron...
Article
Dynamic chromatin behavior plays a critical role in various genome functions. However, it remains unclear how chromatin behavior changes during interphase, where the nucleus enlarges and genomic DNA doubles. While the previously reported chromatin movements varied during interphase when measured using a minute or longer time scale, we unveil that l...
Article
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 st...
Article
Full-text available
The review begins with a concise description of the principles of phase separation. This is followed by a comprehensive section on phase separation of chromatin, in which we recount the 60 years history of chromatin aggregation studies, discuss the evidence that chromatin aggregation intrinsically is a physiologically relevant liquid–solid phase se...
Article
Full-text available
Background Knowing chromatin components at a DNA regulatory element at any given time is essential for understanding how the element works during cellular proliferation, differentiation and development. A region-specific chromatin purification is an invaluable approach to dissecting the comprehensive chromatin composition at a particular region. Se...
Article
Full-text available
Chromatin in eukaryotic cells is a negatively charged long polymer consisting of DNA, histones, and various associated proteins. With its highly charged and heterogeneous nature, chromatin structure varies greatly depending on various factors (e.g. chemical modifications and protein enrichment) and the surrounding environment (e.g. cations): from a...
Article
Full-text available
DNA loops can be formed by a mechanism in which the cohesin complex pulls DNA strands through its ring structure using biased Brownian motion.
Article
We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover...
Article
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., ca...
Article
Full-text available
Liquid droplets formed inside the cell by liquid–liquid phase separation maintain membrane-less condensates/bodies (or compartments). These droplets are important for concentrating certain molecules and facilitating spatiotemporal regulation of cellular functions. 1,6-hexanediol (1,6-HD), an aliphatic alcohol, inhibits weak hydrophobic protein–prot...
Article
Full-text available
Coherent x-ray diffraction microscopy is a lensless phase-contrast imaging technique with high image contrast. Although electron tomography allows intensive study of the three-dimensional structure of cellular organelles, it has inherent difficulty with thick objects. X rays have the unique benefit of allowing noninvasive analysis of thicker object...
Article
Full-text available
The nucleolus is a nuclear body with multiphase liquid droplets for ribosomal RNA (rRNA) transcription. How rRNA transcription is regulated in the droplets remains unclear. Here, using single-molecule tracking of RNA poly-merase I (Pol I) and chromatin-bound upstream binding factor (UBF), we reveal suppression of transcription with phase separation...
Article
Full-text available
The nucleolus is a nuclear body with multiphase liquid droplets for ribosomal RNA (rRNA) transcription. How rRNA transcription is regulated in the droplets remains unclear. Here, using single-molecule tracking of RNA polymerase I (Pol I) and chromatin-bound upstream binding factor (UBF), we reveal suppression of transcription with phase separation....
Article
Full-text available
Eukaryotic chromatin is a negatively charged polymer consisting of genomic DNA, histones, and various nonhistone proteins. Because of its highly charged character, the structure of chromatin varies greatly depending on the surrounding environment (i.e. cations etc.): from an extended 10-nm fiber, to a folded 30-nm fiber, to chromatin condensates/li...
Article
The desire to see the smallest possible objects, such as the contents of cells, reflects our intellectual curiosity and has resulted in the development of various types of microscopes. Microscopes using an X-ray source were developed after Röntgen’s discovery of X-rays in 1895. Röntgen rays were first used for photography in 1896 and for observatio...
Article
Eukaryotic chromatin is a complex of genome DNA and associated proteins, and its structure and dynamics play a crucial role in regulating DNA functions. Chromatin takes rather irregular structures in the nucleus and exhibits heterogeneous sub-diffusive movements as polymers fluctuating in a fluid state. Using genome-wide single-nucleosome tracking...
Article
Eukaryotic chromatin is a complex of nucleic acids and proteins that is central to interpreting the information coded in the genome. Chromatin is rather irregularly folded inside the nucleus in a fluid-like state that exhibits dynamic local movement. The highly dynamic nature of chromatin has become increasingly appreciated, particularly in DNA-tem...
Article
Full-text available
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...
Preprint
Full-text available
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. Bi-modal nature of the mean squared displacement distribution of nucleosomes allows for a natural categorization of th...
Preprint
Full-text available
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. Bi-modal nature of the mean squared displacement distribution of nucleosomes allows for a natural categorization of th...
Article
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...
Article
Full-text available
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...
Article
Full-text available
Although chromatin organization and dynamics play a critical role in gene transcription, how they interplay remains unclear. To approach this issue, we investigated genome-wide chromatin behavior under various transcriptional conditions in living human cells using single-nucleosome imaging. While transcription by RNA polymerase II (RNAPII) is gener...
Article
Full-text available
The nucleus in eukaryotic cells is the site for genomic functions such as RNA transcription, DNA replication, and DNA repair/recombination. However, the nucleus is subjected to various mechanical forces associated with diverse cellular activities, including contraction, migration, and adhesion. Although it has long been assumed that the lamina stru...
Article
Full-text available
Condensins are key players in mitotic chromosome condensation. Using an elegant combination of state-of-the-art imaging techniques, Walther et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201801048) counted the number of Condensins, examined their behaviors on human mitotic chromosomes, and integrated the quantitative data to propose a new...
Article
Full-text available
For cell division, negatively charged chromatin, in which nucleosome fibers (10 nm fibers) are irregularly folded [1–5], must be condensed into chromosomes and segregated. While condensin and other proteins are critical for organizing chromatin into the appro- priate chromosome shape [6–17], free divalent cations such as Mg2+ and Ca2+, which conden...
Chapter
Our cells contain a nucleus with an incredibly small volume of ~ 1 picoliter (10⁻¹², or one trillionth), inside which 2 m of genomic DNA is folded. There are two sets of this genomic DNA in the cell. How is genomic DNA stored in the cell? Also, how is information from specific genes searched for and retrieved? This issue is the most basic example o...
Chapter
The manner in which long genomic DNA sequences are organized and behave in living cells remains a fundamental question in biology. To address this question, we carried out single-nucleosome imaging using super-resolution microscopy (photoactivated localization microscopy). We found a large degree of nucleosome movement (or fluctuation) in living ma...
Article
Full-text available
A chromosome is a single long DNA molecule assembled along its length with nucleosomes and proteins. During interphase, a mammalian chromosome exists as a highly organized supramolecular globule in the nucleus. Here, we discuss new insights into how genomic DNA is packaged and organized within interphase chromosomes. Our emphasis is on the structur...
Article
Full-text available
In eukaryotic cells, highly condensed inactive/silenced chromatin has long been called "heterochromatin." However, recent research suggests that such regions are in fact not fully transcriptionally silent, and that there exists only a moderate access barrier to heterochromatin. To further investigate this issue, it is critical to elucidate the phys...
Article
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-nucleos...
Preprint
Full-text available
The genome is three-dimensionally organized in the cell, and the mammalian genome DNA is partitioned into submegabase-sized chromatin domains. Genome functions are regulated within and across the domains according to their organization, whereas the chromatin itself is highly dynamic. However, the details of such dynamic organization of chromatin do...
Article
Full-text available
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 unde...
Article
Full-text available
The genome is three-dimensionally organized in the cell, and the mammalian genome DNA is partitioned into submegabase-sized chromatin domains. Genome functions are regulated within and across the domains according to their organization, whereas the chromatin itself is highly dynamic. However, the details of such dynamic organization of chromatin do...
Article
Full-text available
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 nucleosome...
Data
Plots of the MSD (Fig 2E) on log-log scale. (EPS)
Data
The function Cdf,α of the fractal dimension df for α = 0.6, 0.7, 0.8, 0.9, and 1.0. α has only a slight effect on Cdf,α. (EPS)
Data
Further details on derivations of the theoretical results and remarks on the hydrodynamic effect for the model. (PDF)
Data
The number of tracked trajectories Mi and the standard error of the mean (SEM) of the MSD at the nuclear interior region and the periphery region. The measurements at each region were performed using 10 cells. (PDF)
Data
A schematic representation for nuclear interior (Top left) and periphery (Top right) imaging. Illumination laser (green) and focal plane (red) in the living cells are shown. Note that the two different focal planes were precisely verified by nuclear surface labeling with Nup107 (a nuclear pore component)-Venus (a bright yellow fluorescent protein)...
Article
Synthetic molecules that bind sequence-specifically to DNA have been developed for varied biological applications, including anticancer activity, regulation of gene expression, and visualization of specific genomic regions. Increasing the number of base pairs targeted by synthetic molecules strengthens their sequence specificity. Our group has been...
Preprint
Full-text available
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 nucleosome...
Article
Mammalian mitotic chromosome morphogenesis was analyzed by 4D live-cell and snapshot deconvolution fluorescence imaging. Prophase chromosomes, whose organization was previously unknown, are revealed to comprise co-oriented sister linear loop arrays displayed along a single, peripheral, regularly kinked topoisomerase II/cohesin/condensin II axis. Th...
Article
Full-text available
Genetic information, which is stored in the long strand of genomic DNA as chromatin, must be scanned and read out by various transcription factors. First, gene-specific transcription factors, which are relatively small (∼50 kDa), scan the genome and bind regulatory elements. Such factors then recruit general transcription factors, Mediators, RNA po...
Article
Full-text available
The binding of molecules to specific DNA sequences is important for imaging genome DNA and for studying gene expression. Increasing the number of base pairs targeted by these molecules would provide greater specificity. N-Methylpyrrole-N-methylimidazole (Py-Im) polyamides are one type of such molecules and can bind to the minor groove of DNA in a s...
Article
It remains unclear how the 2 m of human genomic DNA is organized in each cell. The textbook model has long assumed that the 11-nm-diameter nucleosome fiber (beads-on-a-string), in which DNA is wrapped around core histones, is folded into a 30-nm chromatin fiber. One of the classical models assumes that the 30-nm chromatin fiber is further folded he...