Fig 2
Schematics of chromatin-chromatin ES interactions, with a positive-negative charge zipper along the fiber–fiber contact. In the model, a continuous spiral of negative charges represents a super-helix of NCPs (in red ) and a uniform positively charged fiber “background” mimics the histone tails, linker histones, and weakly bound DNA counterions (in blue )
Source publication
Chromatin domains formed in vivo are characterized by different types of 3D
organization of interconnected nucleosomes and architectural proteins. Here, we quantitatively
test a hypothesis that the similarities in the structure of chromatin fibers (which
we call “structural homology”) can affect their mutual electrostatic and protein-mediated
bridg...
Contexts in source publication
Context 1
... λ D is the Debye screening length in the solution, ε = 80 is the solvent dielectric constant, κ n = 1 /λ 2 D + ( 2 π n / H ) 2 is the effective reciprocal screening length of the n th harmonic, H ∼ 110 Å is the average fiber pitch; σ ̄ is the bare negative surface charge density of the fiber and θ is the fraction of the fiber charge compensated by bound basic histone proteins and counterions adsorbed from the solution (all assumed in the model to be uniformly distributed on the fiber surface). For the derivation from the linear Poisson-Boltzmann theory, we address the reader to the original papers [49, 63], where the interaction potential between spiral B-DNA duplexes has been derived. For chromatin–chromatin ES interactions, these expressions can be used [63, 65–69]. The only term in a n that needs to be modified is the so-called “interaction structure factor” f that is responsible for structure-mediated effects [65]. The first term in (1), a 0 provides the energy of ES repulsion of uniformly charged fibers, while the a 1 -term describes the helix-mediated force as a function on the mutual azimuthal angle between the fibers, δφ . The a 1 , 2 terms depend crucially on the helical structure of the fiber. For single-helix, well-separated fibers, the optimal mutual angle is δφ = 0 in the model [65]. Often, at biologically relevant conditions, the contribution of the third term in (1) can be neglected, because of a shorter screening length (see below) and smaller magnitude, a 2 << a 1 . The a 0 term is a function of the fiber charge neutralization fraction θ , a 0 ∝ ( 1 − θ) 2 , while the harmonics a 1 , 2 depend upon the charge pattern on the chromatin fiber. In the model of Fig. 2, the NCPs are arranged into an ideal spiral of pitch H , while positive charges of histone tails, linker histones, and loosely bound cations from the solution are assumed to be distributed uniformly. For simplicity, we model the helical arrangement of NCP “charge centers” as a continuous thin helix of negative charges (red spirals in Fig. 2). One can incorporate a finite thickness of this spiral via a smearing Debye-Waller term in the structure factor that will diminish the magnitude of ES interactions [13]. Similarly, the roughness/randomness in the fiber radius r + r results in the same diminishing factor exp − n 2 2 π 2 < r 2 > for the helical harmonics with n = 1,2, see [65, 70]. Also, each H 4 NCP can be treated in the model as a point-like or smeared localized charge, with a magnitude given by the net charge of histone core proteins and wrapped DNA. Therefore, the concepts of the theory of DNA–DNA ES interactions [49, 65] can be implemented here for chromatin–chromatin ES forces. The variation of interaction coefficients with the radius of a one-start helical chromatin fiber is illustrated in Fig. 3. A typical value for the fiber pitch H = 110 Å was used to represent a dense axial packing of NCPs. In this plot, the fiber surface charge density corresponds to a single-spiral chromatin with ≈ 7 NCPs per helical turn of 11 nm, each NCP with ≈ 50 negative elementary charges e 0 . This value is a realistic estimate for the extent of NCP overcharging by a poly-anionic ≈ 150 bp long DNA fragment wrapped around the histone core (namely, ∼ + 200 ÷ 250 e 0 charges on the core and ∼ − 300 e 0 on the DNA [71–73]). As compared to DNA–DNA ES forces (see Fig. 1 in [68]), for a fiber radius of r = 15 nm, the interaction harmonics are much larger because of a larger contact area and a higher linear charge density of chromatin fibers. As expected, the interaction harmonics decay nearly exponentially with the fiber–fiber distance, see Fig. 3. ES attraction between chromatin segments is realized when ∂ E /∂ R > 0. This attractive branch of the potential is often accompanied by the condition a 1 > a 0 + a 2 for the interaction harmonics. Such attraction between net similarly charged helices occurs via the charge zipper mechanism pioneered for the two ideally helical DNA duplexes in [49] and due to the same physical nature for chromatin fibers. Namely, at a proper azimuthal alignment of δφ = 0, a negative NCP-rich region on one chromatin fiber faces a positively charged NCP-poor “patch” on the neighboring fiber (see Fig. 2). This short-ranged structure-induced charge matching, described for helices by a 1 term in (1) [14], can overwhelm the Debye-Hückel ES repulsion inevitable for net-charged objects (the a 0 term). The interaction energy for ideal helices of length L is then For single-stranded helices, one can often neglect the a 2 -term in (1). Since a 0 ∝ ( 1 − θ ) 2 , the region of fiber–fiber attraction is the widest at θ = 1 for fully neutralized fibers. As the fraction θ is not well known, in Fig. 4 we present the phase diagram of fiber–fiber attraction as obtained from this ES model for varying θ . It illustrates that the region of strongest attraction mediated by helix–helix ES cohesion is located in the region when the fiber–fiber distance is ∼ λ D . The attraction–repulsion transition curves (thick curve) for the fibers of different diameters (e.g., 20, 30, and 40 nm) almost superimpose (not shown). Figure 4 also illustrates that a minimal θ value is required to trigger the attraction, when fiber surfaces are just 1–2 ∼ λ D away from each other. Helix– helix ES zipper attraction is the strongest in this region ...
Context 2
... λ D is the Debye screening length in the solution, ε = 80 is the solvent dielectric constant, κ n = 1 /λ 2 D + ( 2 π n / H ) 2 is the effective reciprocal screening length of the n th harmonic, H ∼ 110 Å is the average fiber pitch; σ ̄ is the bare negative surface charge density of the fiber and θ is the fraction of the fiber charge compensated by bound basic histone proteins and counterions adsorbed from the solution (all assumed in the model to be uniformly distributed on the fiber surface). For the derivation from the linear Poisson-Boltzmann theory, we address the reader to the original papers [49, 63], where the interaction potential between spiral B-DNA duplexes has been derived. For chromatin–chromatin ES interactions, these expressions can be used [63, 65–69]. The only term in a n that needs to be modified is the so-called “interaction structure factor” f that is responsible for structure-mediated effects [65]. The first term in (1), a 0 provides the energy of ES repulsion of uniformly charged fibers, while the a 1 -term describes the helix-mediated force as a function on the mutual azimuthal angle between the fibers, δφ . The a 1 , 2 terms depend crucially on the helical structure of the fiber. For single-helix, well-separated fibers, the optimal mutual angle is δφ = 0 in the model [65]. Often, at biologically relevant conditions, the contribution of the third term in (1) can be neglected, because of a shorter screening length (see below) and smaller magnitude, a 2 << a 1 . The a 0 term is a function of the fiber charge neutralization fraction θ , a 0 ∝ ( 1 − θ) 2 , while the harmonics a 1 , 2 depend upon the charge pattern on the chromatin fiber. In the model of Fig. 2, the NCPs are arranged into an ideal spiral of pitch H , while positive charges of histone tails, linker histones, and loosely bound cations from the solution are assumed to be distributed uniformly. For simplicity, we model the helical arrangement of NCP “charge centers” as a continuous thin helix of negative charges (red spirals in Fig. 2). One can incorporate a finite thickness of this spiral via a smearing Debye-Waller term in the structure factor that will diminish the magnitude of ES interactions [13]. Similarly, the roughness/randomness in the fiber radius r + r results in the same diminishing factor exp − n 2 2 π 2 < r 2 > for the helical harmonics with n = 1,2, see [65, 70]. Also, each H 4 NCP can be treated in the model as a point-like or smeared localized charge, with a magnitude given by the net charge of histone core proteins and wrapped DNA. Therefore, the concepts of the theory of DNA–DNA ES interactions [49, 65] can be implemented here for chromatin–chromatin ES forces. The variation of interaction coefficients with the radius of a one-start helical chromatin fiber is illustrated in Fig. 3. A typical value for the fiber pitch H = 110 Å was used to represent a dense axial packing of NCPs. In this plot, the fiber surface charge density corresponds to a single-spiral chromatin with ≈ 7 NCPs per helical turn of 11 nm, each NCP with ≈ 50 negative elementary charges e 0 . This value is a realistic estimate for the extent of NCP overcharging by a poly-anionic ≈ 150 bp long DNA fragment wrapped around the histone core (namely, ∼ + 200 ÷ 250 e 0 charges on the core and ∼ − 300 e 0 on the DNA [71–73]). As compared to DNA–DNA ES forces (see Fig. 1 in [68]), for a fiber radius of r = 15 nm, the interaction harmonics are much larger because of a larger contact area and a higher linear charge density of chromatin fibers. As expected, the interaction harmonics decay nearly exponentially with the fiber–fiber distance, see Fig. 3. ES attraction between chromatin segments is realized when ∂ E /∂ R > 0. This attractive branch of the potential is often accompanied by the condition a 1 > a 0 + a 2 for the interaction harmonics. Such attraction between net similarly charged helices occurs via the charge zipper mechanism pioneered for the two ideally helical DNA duplexes in [49] and due to the same physical nature for chromatin fibers. Namely, at a proper azimuthal alignment of δφ = 0, a negative NCP-rich region on one chromatin fiber faces a positively charged NCP-poor “patch” on the neighboring fiber (see Fig. 2). This short-ranged structure-induced charge matching, described for helices by a 1 term in (1) [14], can overwhelm the Debye-Hückel ES repulsion inevitable for net-charged objects (the a 0 term). The interaction energy for ideal helices of length L is then For single-stranded helices, one can often neglect the a 2 -term in (1). Since a 0 ∝ ( 1 − θ ) 2 , the region of fiber–fiber attraction is the widest at θ = 1 for fully neutralized fibers. As the fraction θ is not well known, in Fig. 4 we present the phase diagram of fiber–fiber attraction as obtained from this ES model for varying θ . It illustrates that the region of strongest attraction mediated by helix–helix ES cohesion is located in the region when the fiber–fiber distance is ∼ λ D . The attraction–repulsion transition curves (thick curve) for the fibers of different diameters (e.g., 20, 30, and 40 nm) almost superimpose (not shown). Figure 4 also illustrates that a minimal θ value is required to trigger the attraction, when fiber surfaces are just 1–2 ∼ λ D away from each other. Helix– helix ES zipper attraction is the strongest in this region ...
Context 3
... λ D is the Debye screening length in the solution, ε = 80 is the solvent dielectric constant, κ n = 1 /λ 2 D + ( 2 π n / H ) 2 is the effective reciprocal screening length of the n th harmonic, H ∼ 110 Å is the average fiber pitch; σ ̄ is the bare negative surface charge density of the fiber and θ is the fraction of the fiber charge compensated by bound basic histone proteins and counterions adsorbed from the solution (all assumed in the model to be uniformly distributed on the fiber surface). For the derivation from the linear Poisson-Boltzmann theory, we address the reader to the original papers [49, 63], where the interaction potential between spiral B-DNA duplexes has been derived. For chromatin–chromatin ES interactions, these expressions can be used [63, 65–69]. The only term in a n that needs to be modified is the so-called “interaction structure factor” f that is responsible for structure-mediated effects [65]. The first term in (1), a 0 provides the energy of ES repulsion of uniformly charged fibers, while the a 1 -term describes the helix-mediated force as a function on the mutual azimuthal angle between the fibers, δφ . The a 1 , 2 terms depend crucially on the helical structure of the fiber. For single-helix, well-separated fibers, the optimal mutual angle is δφ = 0 in the model [65]. Often, at biologically relevant conditions, the contribution of the third term in (1) can be neglected, because of a shorter screening length (see below) and smaller magnitude, a 2 << a 1 . The a 0 term is a function of the fiber charge neutralization fraction θ , a 0 ∝ ( 1 − θ) 2 , while the harmonics a 1 , 2 depend upon the charge pattern on the chromatin fiber. In the model of Fig. 2, the NCPs are arranged into an ideal spiral of pitch H , while positive charges of histone tails, linker histones, and loosely bound cations from the solution are assumed to be distributed uniformly. For simplicity, we model the helical arrangement of NCP “charge centers” as a continuous thin helix of negative charges (red spirals in Fig. 2). One can incorporate a finite thickness of this spiral via a smearing Debye-Waller term in the structure factor that will diminish the magnitude of ES interactions [13]. Similarly, the roughness/randomness in the fiber radius r + r results in the same diminishing factor exp − n 2 2 π 2 < r 2 > for the helical harmonics with n = 1,2, see [65, 70]. Also, each H 4 NCP can be treated in the model as a point-like or smeared localized charge, with a magnitude given by the net charge of histone core proteins and wrapped DNA. Therefore, the concepts of the theory of DNA–DNA ES interactions [49, 65] can be implemented here for chromatin–chromatin ES forces. The variation of interaction coefficients with the radius of a one-start helical chromatin fiber is illustrated in Fig. 3. A typical value for the fiber pitch H = 110 Å was used to represent a dense axial packing of NCPs. In this plot, the fiber surface charge density corresponds to a single-spiral chromatin with ≈ 7 NCPs per helical turn of 11 nm, each NCP with ≈ 50 negative elementary charges e 0 . This value is a realistic estimate for the extent of NCP overcharging by a poly-anionic ≈ 150 bp long DNA fragment wrapped around the histone core (namely, ∼ + 200 ÷ 250 e 0 charges on the core and ∼ − 300 e 0 on the DNA [71–73]). As compared to DNA–DNA ES forces (see Fig. 1 in [68]), for a fiber radius of r = 15 nm, the interaction harmonics are much larger because of a larger contact area and a higher linear charge density of chromatin fibers. As expected, the interaction harmonics decay nearly exponentially with the fiber–fiber distance, see Fig. 3. ES attraction between chromatin segments is realized when ∂ E /∂ R > 0. This attractive branch of the potential is often accompanied by the condition a 1 > a 0 + a 2 for the interaction harmonics. Such attraction between net similarly charged helices occurs via the charge zipper mechanism pioneered for the two ideally helical DNA duplexes in [49] and due to the same physical nature for chromatin fibers. Namely, at a proper azimuthal alignment of δφ = 0, a negative NCP-rich region on one chromatin fiber faces a positively charged NCP-poor “patch” on the neighboring fiber (see Fig. 2). This short-ranged structure-induced charge matching, described for helices by a 1 term in (1) [14], can overwhelm the Debye-Hückel ES repulsion inevitable for net-charged objects (the a 0 term). The interaction energy for ideal helices of length L is then For single-stranded helices, one can often neglect the a 2 -term in (1). Since a 0 ∝ ( 1 − θ ) 2 , the region of fiber–fiber attraction is the widest at θ = 1 for fully neutralized fibers. As the fraction θ is not well known, in Fig. 4 we present the phase diagram of fiber–fiber attraction as obtained from this ES model for varying θ . It illustrates that the region of strongest attraction mediated by helix–helix ES cohesion is located in the region when the fiber–fiber distance is ∼ λ D . The attraction–repulsion transition curves (thick curve) for the fibers of different diameters (e.g., 20, 30, and 40 nm) almost superimpose (not shown). Figure 4 also illustrates that a minimal θ value is required to trigger the attraction, when fiber surfaces are just 1–2 ∼ λ D away from each other. Helix– helix ES zipper attraction is the strongest in this region ...
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Citations
... Differing sensitivity of (bio)chemical processes to different chirality is termed 'enantioselectivity'. It is a matter of contemporary research as to how enantioselectivity affects molecular interactions [15,16] and functions [17,18] in biological systems. The interest is driven in significant part by interest in the design and synthesis of drug molecules for the reason mentioned above. ...
The vibration theory of olfaction, which explains it as the sensing of odorant molecules by their vibrational energies through inelastic electron tunnelling spectroscopy (IETS) has inspired olfactory sensor ideas. However, this theory has been presumed inadequate to explain the difference in smell between enantiomers (chiral molecules, which are mirror images of each other), since these have identical vibrational spectra. Going beyond phenomenological assumptions of enantioselective tunnelling, we show on the basis of ab initio modelling of real chiral molecules, that this drawback is indeed obviated for IETS-based olfactory sensors if they are chiral. Our treatment unifies IETS with chirality induced spin selectivity, which explains that charge polarization in chiral molecules by accompanied by spin polarization. First, we apply ab initio symmetry adapted perturbation theory to explain and illustrate enantioselective coupling of chiral odorant molecules and chiral olfactory sensors. This naturally leads to enantioselective coupling of the vibrational mode of an odorant to electron transport (electron-vibron coupling) in an IETS-based sensor when both odorant and sensor are chiral. Finally, we show, from phenomenological quantum transport calculations, that that in turn results in enantioselective IET spectra. Thus, we have demonstrated the feasibility of enantioselective sensing within a vibration framework. Our work also limns the possibility of quantum biomimetic electronic nose sensors that are enantioselective, a feature which could open up new sensing applications.
... In his presentation, Michael Hausmann (M.H.) went back to the early assumption of Erwin Schrödinger [135] that chromatin acts like an "aperiodic solid state within a limited volume," and showed that the consequences of chromatin self-organization [136,137] in the limited volume of the cell nucleus are functionally determined networks [7] (e.g., heterochromatin network [36], network of ALU regions [138,139], network of L1 regions [139], etc.) and local topologies. Within these networks, chromatin architecture is rearranged during cell fate [41] and under environmental stress (e.g., radiation response) and interacts with epigenetic activities and feedback loops [140]. ...
Complex functioning of the genome in the cell nucleus is controlled at different levels: (a) the DNA base sequence containing all relevant inherited information; (b) epigenetic pathways consisting of protein interactions and feedback loops; (c) the genome architecture and organization activating or suppressing genetic interactions between different parts of the genome. Most research so far has shed light on the puzzle pieces at these levels. This article, however, attempts an integrative approach to genome expression regulation incorporating these different layers. Under environmental stress or during cell development, differentiation towards specialized cell types, or to dysfunctional tumor, the cell nucleus seems to react as a whole through coordinated changes at all levels of control. This implies the need for a framework in which biological, chemical, and physical manifestations can serve as a basis for a coherent theory of gene self-organization. An international symposium held at the Biomedical Research and Study Center in Riga, Latvia, on 25 July 2022 addressed novel aspects of the abovementioned topic. The present article reviews the most recent results and conclusions of the state-of-the-art research in this multidisciplinary field of science, which were delivered and discussed by scholars at the Riga symposium.
... Although these compounds may have weak mutual affinity only, they may zipper up, because identical irregular shapes would regularly follow adjacent paths like curly hair strands follow the same curling rather than an individually different one. Such alignments result in stable structures of low potential energy (Henikoff 1995;Cherstvy and Teif 2013). Consequently, biological complex systems like chromatin in a cell nucleus, full of other proteins, molecules, and ions, adapt to this environment by the formation of "networks" of identical compounds which cluster in spatial domains (Singh and Huskinsson 1998;Nishikawa and Ohyama 2013;Bizzarri et al. 2020;Uversky and Giuliani 2021). ...
The cell nucleus is a complex biological system in which simultaneous reactions and functions take place to keep the cell as an individualized, specialized system running well. The cell nucleus contains chromatin packed in various degrees of density and separated in volumes of chromosome territories and subchromosomal domains. Between the chromatin, however, there is enough “free” space for floating RNA, proteins, enzymes, ATPs, ions, water molecules, etc. which are trafficking by super- and supra-diffusion to the interaction points where they are required. It seems that this trafficking works somehow automatically and drives the system perfectly. After exposure to ionizing radiation causing DNA damage from single base damage up to chromatin double-strand breaks, the whole system “cell nucleus” responds, and repair processes are starting to recover the fully functional and intact system. In molecular biology, many individual epigenetic pathways of DNA damage response or repair of single and double-strand breaks are described. How these responses are embedded into the response of the system as a whole is often out of the focus of consideration. In this article, we want to follow the hypothesis of chromatin architecture’s impact on epigenetic pathways and vice versa. Based on the assumption that chromatin acts like an “aperiodic solid state within a limited volume,” functionally determined networks and local topologies (“islands”) can be defined that drive the appropriate repair process at a given damage site. Experimental results of investigations of the chromatin nano-architecture and DNA repair clusters obtained by means of single-molecule localization microscopy offer hints and perspectives that may contribute to verifying the hypothesis.KeywordsAperiodic solid stateNetworks of chromatinRegulatory impact of genome architectureSingle-molecule localization microscopyGeometry and topology of repair foci
... Most likely, it is impossible to describe the structure of chromatin only by these two classes, visible through an optical microscope. If we consider the factor of structural homology, which is characteristic of heterochromatin, then this structuredness must and probably will certainly affect the fractal dimension of chromatin [40]. However, in euchromatin, according to [40], there are very small structurally homologous regions in parallel with intermediate states. ...
... If we consider the factor of structural homology, which is characteristic of heterochromatin, then this structuredness must and probably will certainly affect the fractal dimension of chromatin [40]. However, in euchromatin, according to [40], there are very small structurally homologous regions in parallel with intermediate states. So structural homology is characteristic of both types of chromatin. ...
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... Replication timing information is concealed by corresponding epigenetic histone modifications for particular nucleosome conformation states, which are known as setting the same chromatin marks of the DNA segments replicating at the same time [154,156]. This enables their spatial assembly by nucleosome conformation complementarity in interphase [157,158]. The epigenetic histone setting may provide the epigenetic memory that is stable through the cell cycles [159,160]. ...
Open systems can only exist by self-organization as pulsing structures exchanging matter and energy with the outer world. This review is an attempt to reveal the organizational principles of the heterochromatin supra-intra-chromosomal network in terms of nonlinear thermodynamics. The accessibility of the linear information of the genetic code is regulated by constitutive heterochromatin (CHR) creating the positional information in a system of coordinates. These features include scale-free splitting-fusing of CHR with the boundary constraints of the nucleolus and nuclear envelope. The analysis of both the literature and our own data suggests a radial-concentric network as the main structural organization principle of CHR regulating transcriptional pulsing. The dynamic CHR network is likely created together with nucleolus-associated chromatin domains, while the alveoli of this network, including springy splicing speckles, are the pulsing transcription hubs. CHR contributes to this regulation due to the silencing position variegation effect, stickiness, and flexible rigidity determined by the positioning of nucleosomes. The whole system acts in concert with the elastic nuclear actomyosin network which also emerges by self-organization during the transcriptional pulsing process. We hypothesize that the the transcriptional pulsing, in turn, adjusts its frequency/amplitudes specified by topologically associating domains to the replication timing code that determines epigenetic differentiation memory.
... A possibility of recognition of structurally homologous chromatin fibres has previously been considered in [34]. The study led to the conclusion that long-range recognition is facilitated by protein bridging interactions; when closely juxtaposed, direct electrostatic recognition enables finetuned structure-specific recognition. ...
One of the least understood properties of chromatin is the ability of its similar regions to recognize each other through weak interactions. Theories based on electrostatic interactions between helical macromolecules suggest that the ability to recognize sequence homology is an innate property of the non-ideal helical structure of DNA. However, this theory does not account for the nucleosomal packing of DNA. Can homologous DNA sequences recognize each other while wrapped up in the nucleosomes? Can structural homology arise at the level of nucleosome arrays? Here, we present a theoretical model for the recognition potential well between chromatin fibres sliding against each other. This well is different from the one predicted for bare DNA; the minima in energy do not correspond to literal juxtaposition, but are shifted by approximately half the nucleosome repeat length. The presence of this potential well suggests that nucleosome positioning may induce mutual sequence recognition between chromatin fibres and facilitate the formation of chromatin nanodomains. This has implications for nucleosome arrays enclosed between CTCF–cohesin boundaries, which may form stiffer stem-like structures instead of flexible entropically favourable loops. We also consider switches between chromatin states, e.g. through acetylation/deacetylation of histones, and discuss nucleosome-induced recognition as a precursory stage of genetic recombination.
... From this, we can obtain the relevant interaction energies and hence investigate the 'histone-on' homology recognition well, and its implications for these biological effects. A possibility of recognition of structurally homologous chromatin fibers has previously been considered by Cherstvy & Teif 34 . This study led to the conclusion that long range recognition is facilitated by protein bridging interactions, and when closely juxtaposed, direct electrostatic recognition enables fine-tuned structurespecific recognition. ...
One of the least understood properties of chromatin is the ability of its similar regions to recognise each other through weak interactions. Theories based on electrostatic interactions between helical macromolecules suggest that the ability to recognize sequence homology is an innate property of the non-ideal helical structure of DNA. However, this theory does not account for nucleosomal packing of DNA. Can homologous DNA sequences recognize each other while wrapped up in the nucleosomes? Can structural homology arise at the level of nucleosome arrays? Here we present a theoretical investigation of the recognition-potential-well between chromatin fibers sliding against each other. This well is different to the one predicted and observed for bare DNA; the minima in energy do not correspond to literal juxtaposition, but are shifted by approximately half the nucleosome repeat length. The presence of this potential-well suggests that nucleosome positioning may induce mutual sequence recognition between chromatin fibers and facilitate formation of chromatin nanodomains. This has implications for nucleosome arrays enclosed between CTCF-cohesin boundaries, which may form stiffer stem-like structures instead of flexible entropically favourable loops. We also consider switches between chromatin states, e.g., through acetylation/deacetylation of histones, and discuss nucleosome-induced recognition as a precursory stage of genetic recombination.
... It can be reasoned that multiplication in polyploid cells of the identical chromosome alleles with the identical epigenetic status of bivalent genes should not just linearly increase their epigenetic effect proportionally to gene dosage but potentiate it by the thermodynamics of structural self-organization (phase transition). The role of the closely-juxtaposed DNA fibres' electrostatic forces yielding fine-tuned structure-specific recognition and pairing [97,98] should also contribute in the chromatin self-organization by polyploidy. A similar thought on the potentiating structural effect of additional DNA by the chromatin modifiers and transcription factors has been proposed earlier [99,100]. ...
Tumours were recently revealed to undergo a phylostratic and phenotypic shift to unicellularity. As well, aggressive tumours are characterized by an increased proportion of polyploid cells. In order to investigate a possible shared causation of these two features, we performed a comparative phylostratigraphic analysis of ploidy-related genes, obtained from transcriptomic data for polyploid and diploid human and mouse tissues using pairwise cross-species transcriptome comparison and principal component analysis. Our results indicate that polyploidy shifts the evolutionary age balance of the expressed genes from the late metazoan phylostrata towards the upregulation of unicellular and early metazoan phylostrata. The up-regulation of unicellular metabolic and drug-resistance pathways and the downregulation of pathways related to circadian clock were identified. This evolutionary shift was associated with the enrichment of ploidy with bivalent genes (p < 10 −16). The protein interactome of activated bivalent genes revealed the increase of the connectivity of unicellulars and (early) multicellulars, while circadian regulators were depressed. The mutual polyploidy-c-MYC-bivalent genes-associated protein network was organized by gene-hubs engaged in both embryonic development and metastatic cancer including driver (proto)-oncogenes of viral origin. Our data suggest that, in cancer, the atavistic shift goes hand-in-hand with polyploidy and is driven by epigenetic mechanisms impinging on development-related bivalent genes.
... Finally, in contrast to models considering cation-binding specificity, there have been studies that treated the DNA condensation problem purely in terms of counterion-induced electrostatic attraction between like-charged rods of DNA helixes (45), also known as the ''electrostatic zipper model'' (46). In particular, the peptide sequence homology effect on charge distribution along DNA cylinders was investigated as a possible factor promoting attraction between two DNA helixes (48). It is important to note that binding affinity of a peptide to DNA does not always correlate with its DNA compaction efficiency. ...
Compaction of T4 phage DNA (166 kbp) by short oligopeptide octamers composed of two types of amino acids, four cationic lysine (K), and four polar nonionic serine (S) having different sequence order was studied by single-molecule fluorescent microscopy. We found that efficient DNA compaction by oligopeptide octamers depends on the geometrical match between phosphate groups of DNA and cationic amines. The amino acid sequence order in octamers dramatically affects the mechanism of DNA compaction, which changes from a discrete all-or-nothing coil-globule transition induced by a less efficient (K 4 S 4 ) octamer to a continuous compaction transition induced by a (KS) 4 octamer with a stronger DNA-binding character. This difference in the DNA compaction mechanism dramatically changes the packaging density, and the morphology of T4 DNA condensates: DNA is folded into ordered toroidal or rod morphologies during all-or-nothing compaction, whereas disordered DNA condensates are formed as a result of the continuous DNA compaction. Furthermore, the difference in DNA compaction mechanism has a certain effect on the inhibition scenario of the DNA transcription activity, which is gradual for the continuous DNA compaction and abrupt for the all-or-nothing DNA collapse.
... In addition, some landmark structures of chromosomes such as telomere, centromere and pericentromere regions are concentrated with various repetitive DNAs, indicating a key role of these sequences in formatting chromosomes. Lines of evidence suggest that DNA and chromatins with homologous sequences such as repetitive DNA elements have an intrinsic property/tendency for self-interaction [8][9][10][11][12]. I have formulated the CORE (chromosome organization by repetitive elements) theory to describe the critical roles of repetitive DNA in organizing chromatin folding in the higher-order structure of chromosomes. ...
The basic principles of chromosomal organization in eukaryotic cells remain elusive. Current mainstream research efforts largely concentrate on searching for critical packaging proteins involved in organizing chromosomes. I have taken a different perspective, by considering the role of genomic information in chromatins. In particular, I put forward the concept that repetitive DNA elements are key chromosomal packaging modules, and their intrinsic property of homology-based interaction can drive chromatin folding. Many repetitive DNA families have high copy numbers and clustered distribution patterns in the linear genomes. These features may facilitate the interactions among members in the same repeat families. In this paper, the potential liquid-liquid phase transition of repetitive DNAs that is induced by their extensive interaction in chromosomes will be considered. I propose that the interaction among repetitive DNAs may lead to phase separation of interacting repetitive DNAs from bulk chromatins. Phase separation of repetitive DNA may provide a physical mechanism that drives rapid massive changes of chromosomal conformation.
