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Stacked thin layers of metaphase chromatin explain the geometry of chromosome rearrangements and banding.

ABSTRACT: The three-dimensional organization of tightly condensed chromatin within metaphase chromosomes has been one of the most challenging problems in structural biology since the discovery of the nucleosome. This study shows that chromosome images obtained from typical banded karyotypes and from different multicolour cytogenetic analyses can be used to gain information about the internal structure of chromosomes. Chromatin bands and the connection surfaces in sister chromatid exchanges and in cancer translocations are planar and orthogonal to the chromosome axis. Chromosome stretching produces band splitting and even the thinnest bands are orthogonal and well defined, indicating that short stretches of DNA can occupy completely the chromosome cross-section. These observations impose strong physical constraints on models that attempt to explain chromatin folding in chromosomes. The thin-plate model, which consists of many stacked layers of planar chromatin perpendicular to the chromosome axis, is compatible with the observed orientation of bands, with the existence of thin bands, and with band splitting; it is also compatible with the orthogonal orientation and planar geometry of the connection surfaces in chromosome rearrangements. The results obtained provide a consistent interpretation of the chromosome structural properties that are used in clinical cytogenetics for the diagnosis of hereditary diseases and cancers.

SUBMITTER: Daban JR

PROVIDER: S-EPMC4597206 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Self-assembly of thin plates from micrococcal nuclease-digested chromatin of metaphase chromosomes.

Project description:The three-dimensional organization of the enormously long DNA molecules packaged within metaphase chromosomes has been one of the most elusive problems in structural biology. Chromosomal DNA is associated with histones and different structural models consider that the resulting long chromatin fibers are folded forming loops or more irregular three-dimensional networks. Here, we report that fragments of chromatin fibers obtained from human metaphase chromosomes digested with micrococcal nuclease associate spontaneously forming multilaminar platelike structures. These self-assembled structures are identical to the thin plates found previously in partially denatured chromosomes. Under metaphase ionic conditions, the fragments that are initially folded forming the typical 30-nm chromatin fibers are untwisted and incorporated into growing plates. Large plates can be self-assembled from very short chromatin fragments, indicating that metaphase chromatin has a high tendency to generate plates even when there are many discontinuities in the DNA chain. Self-assembly at 37°C favors the formation of thick plates having many layers. All these results demonstrate conclusively that metaphase chromatin has the intrinsic capacity to self-organize as a multilayered planar structure. A chromosome structure consistent of many stacked layers of planar chromatin avoids random entanglement of DNA, and gives compactness and a high physical consistency to chromatids.

| S-EPMC3414884 | biostudies-other

Metaphase-Chromosome-Organization

Project description:Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two alternative three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell-type-specific organization described previously for non-synchronous cells is restricted to interphase. In metaphase, we identify a homogenous folding state, which is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we find that metaphase Hi-C data is inconsistent with classic hierarchical models, and is instead best described by a linearly-organized longitudinally compressed array of consecutive chromatin loops.

2013-11-05 | E-MTAB-1948 | biostudies-arrayexpress

Human metaphase chromosome consists of randomly arranged chromatin fibres with up to 30-nm diameter.

Project description:During cell division, mitotic chromosomes assemble and are equally distributed into two new daughter cells. The chromosome organisation of the two chromatids is essential for even distribution of genetic materials. Although the 11-nm fibre or nucleosome structure is well-understood as a fundamental fibrous structure of chromosomes, the reports on organisation of 30-nm basic chromatin fibres have been controversial, with debates on the contribution of 30-nm or thicker fibres to the higher order inner structure of chromosomes. Here, we used focused ion beam/scanning electron microscopy (FIB/SEM) to show that both 11-nm and 30-nm fibres are present in the human metaphase chromosome, although the higher-order periodical structure could not be detected under the conditions employed. We directly dissected the chromosome every 10-nm and observed 224 cross-section SEM images. We demonstrated that the chromosome consisted of chromatin fibres of an average diameter of 16.9-nm. The majority of the chromatin fibres had diameters between 5 and 25-nm, while those with 30-nm were in the minority. The reduced packaging ratio of the chromatin fibres was detected at axial regions of each chromatid. Our results provide a strong basis for further discussions on the chromosome higher-order structure.

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Metaphase-Chromosome-Organization

Project description:Metaphase-Chromosome-Organization

| PRJEB4743 | ENA

Highly ordered ultralong magnetic nanowires wrapped in stacked graphene layers.

Project description:We report on the synthesis and magnetic characterization of ultralong (1 cm) arrays of highly ordered coaxial nanowires with nickel cores and graphene stacking shells (also known as metal-filled carbon nanotubes). Carbon-containing nickel nanowires are first grown on a nanograted surface by magnetron sputtering. Then, a post-annealing treatment favors the metal-catalyzed crystallization of carbon into stacked graphene layers rolled around the nickel cores. The observed uniaxial magnetic anisotropy field oriented along the nanowire axis is an indication that the shape anisotropy dominates the dipolar coupling between the wires. We further show that the thermal treatment induces a decrease in the coercivity of the nanowire arrays. This reflects an enhancement of the quality of the nickel nanowires after annealing attributed to a decrease of the roughness of the nickel surface and to a reduction of the defect density. This new type of graphene-ferromagnetic-metal nanowire appears to be an interesting building block for spintronic applications.

| S-EPMC3556984 | biostudies-literature

Ta2N3 nanocrystals grown in Al2O3 thin layers.

Project description:Tantalum nitride nanoparticles (NPs) and cubic bixbyite-type Ta2N3 nanocrystals (NCs) were grown in (Ta-N+Al2O3)/Al2O3 periodic multilayers (MLs) after thermal treatment. The MLs were prepared by magnetron deposition at room temperature and characterized using grazing incidence small-angle X-ray scattering (GISAXS), X-ray reflectivity (XRR), grazing incidence X-ray diffraction (GIXRD), secondary ion mass spectrometry (SIMS) and X-ray photoelectron spectroscopy (XPS). We found amorphous tantalum nitride NPs at 600-800 °C, with a high degree of ordering along the surface normal and short-range ordering within the layers containing tantalum (metallic layers). At an even higher annealing temperature of 900 °C the NPs crystallize in the rare and relatively unexplored Ta2N3 phase. However, the environment, morphology and spatial ordering of the NCs depend on the thickness of the metallic layers. For 12 nm thick metallic layers, the Ta2N3 NCs have an average diameter of 6 nm and they are confined and short-range ordered within the metallic layers. When the metallic layers are thinner, the NCs grow over 20 nm in diameter, show no spatial ordering, while the periodic structure of the ML was completely destroyed. The results presented here demonstrate a self-assembly process of tantalum nitride NPs, the morphological properties of which depend on the preparation conditions. This can be used as a generic procedure to realize highly tunable and designable optical properties of thin films containing transition-metal nitride nanocrystals.

| S-EPMC5669238 | biostudies-literature

Ran is required before metaphase for spindle assembly and chromosome alignment and after metaphase for chromosome segregation and spindle midbody organization.

Project description:The Ran pathway has been shown to have a role in spindle assembly. However, the extent of the role of the Ran pathway in mitosis in vivo is unclear. We report that perturbation of the Ran pathway disrupted multiple steps of mitosis in syncytial Drosophila embryos and uncovered new mitotic processes that are regulated by Ran. During the onset of mitosis, the Ran pathway is required for the production, organization, and targeting of centrosomally nucleated microtubules to chromosomes. However, the role of Ran is not restricted to microtubule organization, because Ran is also required for the alignment of chromosomes at the metaphase plate. In addition, the Ran pathway is required for postmetaphase events, including chromosome segregation and the assembly of the microtubule midbody. The Ran pathway mediates these mitotic events, in part, by facilitating the correct targeting of the kinase Aurora A and the kinesins KLP61F and KLP3A to spindles.

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Infrared nanospectroscopic mapping of a single metaphase chromosome.

Project description:The integrity of the chromatin structure is essential to every process occurring within eukaryotic nuclei. However, there are no reliable tools to decipher the molecular composition of metaphase chromosomes. Here, we have applied infrared nanospectroscopy (AFM-IR) to demonstrate molecular difference between eu- and heterochromatin and generate infrared maps of single metaphase chromosomes revealing detailed information on their molecular composition, with nanometric lateral spatial resolution. AFM-IR coupled with principal component analysis has confirmed that chromosome areas containing euchromatin and heterochromatin are distinguishable based on differences in the degree of methylation. AFM-IR distribution of eu- and heterochromatin was compared to standard fluorescent staining. We demonstrate the ability of our methodology to locate spatially the presence of anticancer drug sites in metaphase chromosomes and cellular nuclei. We show that the anticancer 'rule breaker' platinum compound [Pt[N(p-HC6F4)CH2]2py2] preferentially binds to heterochromatin, forming localized discrete foci due to condensation of DNA interacting with the drug. Given the importance of DNA methylation in the development of nearly all types of cancer, there is potential for infrared nanospectroscopy to be used to detect gene expression/suppression sites in the whole genome and to become an early screening tool for malignancy.

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Designing Thin, Ultrastretchable Electronics with Stacked Circuits and Elastomeric Encapsulation Materials.

Project description:Many recently developed soft, skin-like electronics with high performance circuits and low modulus encapsulation materials can accommodate large bending, stretching, and twisting deformations. Their compliant mechanics also allows for intimate, nonintrusive integration to the curvilinear surfaces of soft biological tissues. By introducing a stacked circuit construct, the functional density of these systems can be greatly improved, yet their desirable mechanics may be compromised due to the increased overall thickness. To address this issue, the results presented here establish design guidelines for optimizing the deformable properties of stretchable electronics with stacked circuit layers. The effects of three contributing factors (i.e., the silicone inter-layer, the composite encapsulation, and the deformable interconnects) on the stretchability of a multilayer system are explored in detail via combined experimental observation, finite element modeling, and theoretical analysis. Finally, an electronic module with optimized design is demonstrated. This highly deformable system can be repetitively folded, twisted, or stretched without observable influences to its electrical functionality. The ultrasoft, thin nature of the module makes it suitable for conformal biointegration.

| S-EPMC5642935 | biostudies-literature

Atomically thin gallium layers from solid-melt exfoliation.

Project description:Among the large number of promising two-dimensional (2D) atomic layer crystals, true metallic layers are rare. Using combined theoretical and experimental approaches, we report on the stability and successful exfoliation of atomically thin "gallenene" sheets on a silicon substrate, which has two distinct atomic arrangements along crystallographic twin directions of the parent ?-gallium. With a weak interface between solid and molten phases of gallium, a solid-melt interface exfoliation technique is developed to extract these layers. Phonon dispersion calculations show that gallenene can be stabilized with bulk gallium lattice parameters. The electronic band structure of gallenene shows a combination of partially filled Dirac cone and the nonlinear dispersive band near the Fermi level, suggesting that gallenene should behave as a metallic layer. Furthermore, it is observed that the strong interaction of gallenene with other 2D semiconductors induces semiconducting to metallic phase transitions in the latter, paving the way for using gallenene as promising metallic contacts in 2D devices.

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