Fractal nature of chromatin organization in interphase chicken erythrocyte nuclei: DNA structure exhibits biphasic fractal properties

Лебедев, Д. В.; Филатов, М. В.; Куклин, А. И.; Исламов, А. Х.; Kentzinger, Emmanuel; Пантина, Р. А.; Toperverg, B. P.; Isaev-Ivanov, V. V.

doi:10.1016/j.febslet.2005.01.052

Cited by 84 publications

(72 citation statements)

References 14 publications

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“…How this is achieved has been revealed by the seminal simulation studies of the collapse of a linear polymer by Grosberg et al [57], which show how a compact "crumpled globule" with fractal properties is formed (a notable example of the value of non-translational research). Experiments and simulations strongly support this fractal manner of packing chromatin in the nucleus [58][59][60][61] (with the exception of yeast), which was suggested earlier by neutron diffraction studies of nuclei [62]. Data from 3C studies of human chromosomes are consistent with a fractal organization, but not with the alternative "equilibrium globule" conformation [58].…”

Section: Packing the Genome Into The Nucleussupporting

confidence: 64%

Structures and functions in the crowded nucleus: new biophysical insights

Hancock

2014

Front. Phys.

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Concepts and methods from the physical sciences have catalyzed remarkable progress in understanding the cell nucleus in recent years. To share this excitement with physicists and encourage their interest in this field, this review offers an overview of how the physics which underlies structures and functions in the nucleus is becoming more clear thanks to methods which have been developed to simulate and study macromolecules, polymers, and colloids. The environment in the nucleus is very crowded with macromolecules, making entropic (depletion) forces major determinants of interactions. Simulation and experiments are consistent with their key role in forming membraneless compartments such as nucleoli, PML and Cajal bodies, and discrete "territories" for chromosomes. The chromosomes, giant linear polyelectrolyte polymers, exist in vivo in a state like a polymer melt. Looped conformations are predicted in crowded conditions, and have been confirmed experimentally and are central to the regulation of gene expression. Polymer theory has revealed how the chromosomes are so highly compacted in the nucleus, forming a "crumpled globule" with fractal properties which avoids knots and entanglements in DNA while allowing facile accessibility for its replication and transcription. Entropic repulsion between looped polymers can explain the confinement of each chromosome to a discrete region of the nucleus. Crowding and looping are predicted to facilitate finding the specific targets of factors which modulate activities of DNA. Simulation shows that entropic effects contribute to finding and repairing potentially lethal double-strand breaks in DNA by increasing the mobility of the broken ends, favoring their juxtaposition for repair. Signaling pathways are strongly influenced by crowding, which favors a processive mode of response (consecutive reactions without releasing substrates). This new information contributes to understanding the sometimes counter-intuitive consequences and the evolutionary advantages of a crowded environment in the nucleus.

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Section: Packing the Genome Into The Nucleussupporting

confidence: 64%

Structures and functions in the crowded nucleus: new biophysical insights

Hancock

2014

Front. Phys.

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“…(17)- (19). They can be used to fit experimental SAS data and distinguish between the type I system (one fractal absorbs the other fractal) and the type II system (nonoverlapping fractals) as described in Sec.…”

Section: Discussionmentioning

confidence: 99%

“…where we put by definition (19) and the exponents τ 1 and τ 2 are related to the corresponding fractal dimensions by Eq. (1).…”

Section: The Interpolating Formula and The Generalized Methods Ofmentioning

confidence: 99%

“…However, experimental SAS papers have reported the dependence of the scattering intensities on the scattering length densities of surrounding solvent or solid matrix, in which the studied structures are immersed. In particular, the crossover positions q c (that is, the points where the power-law scattering exponent changes) can depend on the contrast value [19]. This indicates a multi-phase structure of the sample, and thus a method capable of extracting the structural properties about each phase is needed.…”

Section: Introductionmentioning

confidence: 99%

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Small-angle scattering from multiphase fractals

et al. 2014

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Small-angle scattering (SAS) intensities observed experimentally are often characterized by the presence of successive power-law regimes with various scattering exponents whose values vary from -4 to -1. This usually indicates multiple fractal structures of the sample characterized by different size scales. The existing models explaining the crossover positions (that is, the points where the power-law scattering exponent changes) involve only one contrast parameter, which depends solely on the ratio of the fractal sizes. Here, a model that describes SAS from a multi-phase system with a few contrast parameters is described, and it is shown that the crossover position depends on the scattering length density of each phase. The Stuhrmann contrast variation method is generalized and applied to experimental curves in the vicinity of the crossover point beyond the Guinier region. The contrast variation is applied not to the intensity itself but to the model parameters, which can be found by fitting the experimental data with the suggested interpolation formula. The model supplements the existing two-phase models and gives the simple condition of their inapplicability: if the crossover point depends on the contrast then a two-phase model is not relevant. The developed analysis allows one to answer the qualitative question of whether one fractal 'absorbs' another one or they are both immersed in a surrounding homogeneous medium like a solvent or solid matrix. The models can be applied to experimental SAS data where the absolute value of the scattering exponent of the first power-law regime is higher than that of the subsequent second power-law regime, that is, the scattering curve is 'convex' near the crossover point. As is shown, the crossover position can be very sensitive to contrast variation, which influences significantly the length of the fractal range.

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“…Furthermore, in vitro studies using texture analysis of microscopy images have shown that the topology of chromatin is well represented as a fractal media (12). Likewise, ex vivo analysis of somatic copy number alterations and neutron scattering measurements of isolated nuclei have shown that, across these length scales, chromatin is well described as a fractal media (13)(14)(15). In conjunction, molecular techniques such as chromosomal capture methods [chromosome conformation capture (3C) and high-throughput 3C (Hi-C)] have shown that the higher-order organization of chromatin above single nucleosomes and below the structure of chromosomal territories follows this same power-law fractal organization.…”

Section: Significancementioning

confidence: 99%

Label-free imaging of the native, living cellular nanoarchitecture using partial-wave spectroscopic microscopy

Almassalha

Bauer

Chandler

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The organization of chromatin is a regulator of molecular processes including transcription, replication, and DNA repair. The structures within chromatin that regulate these processes span from the nucleosomal (10-nm) to the chromosomal (>200-nm) levels, with little known about the dynamics of chromatin structure between these scales due to a lack of quantitative imaging technique in live cells. Previous work using partial-wave spectroscopic (PWS) microscopy, a quantitative imaging technique with sensitivity to macromolecular organization between 20 and 200 nm, has shown that transformation of chromatin at these length scales is a fundamental event during carcinogenesis. As the dynamics of chromatin likely play a critical regulatory role in cellular function, it is critical to develop live-cell imaging techniques that can probe the real-time temporal behavior of the chromatin nanoarchitecture. Therefore, we developed a livecell PWS technique that allows high-throughput, label-free study of the causal relationship between nanoscale organization and molecular function in real time. In this work, we use live-cell PWS to study the change in chromatin structure due to DNA damage and expand on the link between metabolic function and the structure of higherorder chromatin. In particular, we studied the temporal changes to chromatin during UV light exposure, show that live-cell DNA-binding dyes induce damage to chromatin within seconds, and demonstrate a direct link between higher-order chromatin structure and mitochondrial membrane potential. Because biological function is tightly paired with structure, live-cell PWS is a powerful tool to study the nanoscale structure-function relationship in live cells.E very cellular and extracellular structure has a complex nanoscale organization ranging from individual macromolecules that are a few nanometers in size (e.g., protein and DNA) to macromolecular assemblies that are tens to hundreds of nanometers in size (e.g., cell membranes, higher-order chromatin structure, cytoskeleton, and extracellular matrix fibers). A major scientific challenge is to understand these macromolecular structures, specifically their function and interactions in structurally and dynamically complex living cellular systems. To meet these goals, the ideal live-cell imaging technology would satisfy six key requirements: being (i) nanoscale sensitive (<200 nm), (ii) label free, (iii) nonperturbing, (iv) quantitative, (v) high throughput, and (vi) molecularly informative.Current approaches are unable to meet all of these criteria alone. The breakthroughs in superresolution fluorescence microscopy (SRM) have enabled new imaging technologies capable of providing unprecedented molecular identification at the highest resolutions currently available in live cells, but require the use of exogenous fluorophores to visualize macromolecular structures (1-3). For some applications, these labels are indispensable to achieve molecular specificity. However, there are significant drawbacks to the exclusive use of molec...

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Fractal nature of chromatin organization in interphase chicken erythrocyte nuclei: DNA structure exhibits biphasic fractal properties

Cited by 84 publications

References 14 publications

Structures and functions in the crowded nucleus: new biophysical insights

Structures and functions in the crowded nucleus: new biophysical insights

Small-angle scattering from multiphase fractals

Label-free imaging of the native, living cellular nanoarchitecture using partial-wave spectroscopic microscopy

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