Physical and data structure of 3D genome

With the textbook view of chromatin folding based on the 30-nm fiber being challenged, it has been proposed that interphase DNA has an irregular 10-nm nucleosome polymer structure whose folding philosophy is unknown. Nevertheless, experimental advances suggest that this irregular packing is associated with many nontrivial physical properties that are puzzling from a polymer physics point of view. Here, we show that the reconciliation of these exotic properties necessitates modularizing three-dimensional genome into tree data structures on top of, and in striking contrast to, the linear topology of DNA double helix. These functional modules need to be connected and isolated by an open backbone that results in porous and heterogeneous packing in a quasi–self-similar manner, as revealed by our electron and optical imaging. Our multiscale theoretical and experimental results suggest the existence of higher-order universal folding principles for a disordered chromatin fiber to avoid entanglement and fulfill its biological functions.

Download Full-text

Physical and data structure of 3D genome

10.1101/596262 ◽

2019 ◽

Cited By ~ 1

Author(s):

Kai Huang ◽

Yue Li ◽

Anne R. Shim ◽

Rikkert J. Nap ◽

Vasundhara Agrawal ◽

...

Keyword(s):

Double Helix ◽

Polymer Physics ◽

Point Of View ◽

Linear Topology ◽

3D Genome ◽

Multi Scale ◽

Chromatin Folding ◽

Tree Data ◽

Dna Double Helix ◽

Striking Contrast

AbstractWith the textbook view of chromatin folding based on the 30nm fiber being challenged, it has been proposed that interphase DNA has an irregular 10nm nucleosome polymer structure whose folding philosophy is unknown. Nevertheless, experimental advances suggested that such irregular packing is associated with many nontrivial physical properties that are puzzling from a polymer physics point of view. Here, we show that the reconciliation of these exotic properties necessitates modularizing 3D genome into tree data structures on top of, and in striking contrast to the linear topology of DNA double helix. Such functional modules need to be connected and isolated by an open backbone that results in porous and heterogeneous packing in a quasi-self-similar manner as revealed by our electron and optical imaging. Our multi-scale theoretical and experimental results suggest the existence of higher-order universal folding principles for a disordered chromatin fiber to avoid entanglement and fulfill its biological functions.

Download Full-text

Symmetry-adapted digital modeling II. The double-helix B-DNA

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273316002758 ◽

2016 ◽

Vol 72 (3) ◽

pp. 312-323 ◽

Cited By ~ 2

Author(s):

A. Janner

Keyword(s):

Dimensional Space ◽

Double Helix ◽

Three Dimensional ◽

Reduction Factor ◽

Lattice Points ◽

Three Dimensions ◽

Coarse Grained ◽

Digital Modeling ◽

Dna Strands ◽

Dna Double Helix

The positions of phosphorus in B-DNA have the remarkable property of occurring (in axial projection) at well defined points in the three-dimensional space of a projected five-dimensional decagonal lattice, subdividing according to the golden mean ratio τ:1:τ [with τ = (1+\sqrt {5})/2] the edges of an enclosing decagon. The corresponding planar integral indicesn1,n2,n3,n4(which are lattice point coordinates) are extended to include the axial indexn5as well, defined for each P position of the double helix with respect to the single decagonal lattice ΛP(aP,cP) withaP= 2.222 Å andcP= 0.676 Å. A finer decagonal lattice Λ(a,c), witha=aP/6 andc=cP, together with a selection of lattice points for each nucleotide with a given indexed P position (so as to define a discrete set in three dimensions) permits the indexing of the atomic positions of the B-DNA d(AGTCAGTCAG) derived by M. J. P. van Dongen. This is done for both DNA strands and the single lattice Λ. Considered first is the sugar–phosphate subsystem, and then each nucleobase guanine, adenine, cytosine and thymine. One gets in this way a digital modeling of d(AGTCAGTCAG) in a one-to-one correspondence between atomic and indexed positions and a maximal deviation of about 0.6 Å (for the value of the lattice parameters given above). It is shown how to get a digital modeling of the B-DNA double helix for any given code. Finally, a short discussion indicates how this procedure can be extended to derive coarse-grained B-DNA models. An example is given with a reduction factor of about 2 in the number of atomic positions. A few remarks about the wider interest of this investigation and possible future developments conclude the paper.

Download Full-text

DNA information: from digital code to analogue structure

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2011.0231 ◽

2012 ◽

Vol 370 (1969) ◽

pp. 2960-2986 ◽

Cited By ~ 29

Author(s):

A. A. Travers ◽

G. Muskhelishvili ◽

J. M. T. Thompson

Keyword(s):

Dimensional Space ◽

Double Helix ◽

Three Dimensional ◽

Base Pairs ◽

Nucleosome Core ◽

Histone Octamer ◽

Regulatory Mode ◽

Sequence Periodicity ◽

Recent Developments ◽

Dna Double Helix

The digital linear coding carried by the base pairs in the DNA double helix is now known to have an important component that acts by altering, along its length, the natural shape and stiffness of the molecule. In this way, one region of DNA is structurally distinguished from another, constituting an additional form of encoded information manifest in three-dimensional space. These shape and stiffness variations help in guiding and facilitating the DNA during its three-dimensional spatial interactions. Such interactions with itself allow communication between genes and enhanced wrapping and histone–octamer binding within the nucleosome core particle. Meanwhile, interactions with proteins can have a reduced entropic binding penalty owing to advantageous sequence-dependent bending anisotropy. Sequence periodicity within the DNA, giving a corresponding structural periodicity of shape and stiffness, also influences the supercoiling of the molecule, which, in turn, plays an important facilitating role. In effect, the super-helical density acts as an analogue regulatory mode in contrast to the more commonly acknowledged purely digital mode. Many of these ideas are still poorly understood, and represent a fundamental and outstanding biological question. This review gives an overview of very recent developments, and hopefully identifies promising future lines of enquiry.

Download Full-text

A Quercetin Biosensor Based on Chitosan-Entrapped Carbon Nanotube Paste Electrode Coated with DNA

Journal of AOAC International ◽

10.5740/jaoacint.15-042 ◽

2015 ◽

Vol 98 (5) ◽

pp. 1375-1381 ◽

Cited By ~ 5

Author(s):

Fatemeh Rezazadeh ◽

Maryam Mohamadi ◽

Daryoush Afzali ◽

Tayebeh Shamspur ◽

Ali Mostafavi

Keyword(s):

Carbon Nanotube ◽

Double Helix ◽

Low Cost ◽

Electrochemical Determination ◽

Point Of View ◽

Analytical Point ◽

Carbon Nanotube Paste Electrode ◽

Anodic Peak Current ◽

Dna Double Helix ◽

Paste Electrode

Abstract This paper presents an easy, fast, low cost, and sensitive approach for the electrochemical determination of quercetin based on its intercalation into DNA double helix. Electrochemical studies of the interaction between quercetin and DNA showed a decrease in peak currents with a reduction in redox reversibility of quercetin in the presence of the DNA. The electrochemical behavior of quercetin at a chitosan-entrapped carbon nanotube paste electrode coated with DNA was studied. A considerable increase was observed in the oxidation signal of quercetin at the DNA-coated electrode compared with a DNA-free electrode, indicating the preconcentration of quercetin due to its interaction with the surface-confined DNA layer. After optimizing the main experimental parameters influencing the biosensor response, its performance was evaluated from an analytical point of view. Two linear dependences of the anodic peak current of quercetin on its concentration were observed in the ranges of 0.40–7.50 and 7.50–30.0 μmol/L, with LOD and LOQ of 0.039 and 0.13 μmol/L, respectively. The proposed biosensor was successfully applied to the analysis of black and green tea extracts for their quercetin content.

Download Full-text

Computer graphics program to reveal the dependence of the gross three-dimensional structure of the B-DNA double helix on primary structure

Nucleic Acids Research ◽

10.1093/nar/14.1.381 ◽

1986 ◽

Vol 14 (1) ◽

pp. 381-387 ◽

Cited By ~ 25

Author(s):

Chang-Shung Tung ◽

Stephen C. Harvey

Keyword(s):

Computer Graphics ◽

Primary Structure ◽

Double Helix ◽

Three Dimensional ◽

Dimensional Structure ◽

Three Dimensional Structure ◽

Dna Double Helix

Download Full-text

Sensitivity Analysis for the Mechanical Properties of DNA Bundles

Journal of Nanomaterials ◽

10.1155/2016/6287937 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Young-Joo Kim ◽

Do-Nyun Kim

Keyword(s):

Mechanical Properties ◽

Sensitivity Analysis ◽

Double Helix ◽

Three Dimensional ◽

Dna Nanotechnology ◽

Structural Features ◽

Structural Motifs ◽

Dimensional Shape ◽

The Individual ◽

Dna Double Helix

In structural DNA nanotechnology, programming a three-dimensional shape into DNA bundles has been a primary design objective. However, the mechanical properties of these DNA bundle structures are another important factor to be considered in the design process. While the mechanics of the individual DNA double helix has been explored extensively and hence its properties are well known, the mechanical properties of structural motifs such as DNA junctions and strand breaks important to bundle mechanics have not been well characterized due to experimental limitations, rendering it difficult to predict the mechanical properties of DNA bundles. Here, we investigate the effect of these structural motifs on the global bundle rigidities by performing sensitivity analysis on a six-helix DNA bundle structure using the finite element modeling approach. Results reveal the primary structural features and their parametric values required to reproduce the experimental bundle rigidities.

Download Full-text

RNA Biogenesis Instructs Functional Inter-Chromosomal Genome Architecture

Frontiers in Genetics ◽

10.3389/fgene.2021.645863 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alessandro Bertero

Keyword(s):

Rna Polymerase Ii ◽

Cardiac Myocyte ◽

Three Dimensional ◽

Mitotic Cell ◽

Genome Architecture ◽

3D Genome ◽

Functional Relationships ◽

Splicing Regulator ◽

Rna Biogenesis ◽

Chromatin Folding

Three-dimensional (3D) genome organization has emerged as an important layer of gene regulation in development and disease. The functional properties of chromatin folding within individual chromosomes (i.e., intra-chromosomal or in cis) have been studied extensively. On the other hand, interactions across different chromosomes (i.e., inter-chromosomal or in trans) have received less attention, being often regarded as background noise or technical artifacts. This viewpoint has been challenged by emerging evidence of functional relationships between specific trans chromatin interactions and epigenetic control, transcription, and splicing. Therefore, it is an intriguing possibility that the key processes involved in the biogenesis of RNAs may both shape and be in turn influenced by inter-chromosomal genome architecture. Here I present the rationale behind this hypothesis, and discuss a potential experimental framework aimed at its formal testing. I present a specific example in the cardiac myocyte, a well-studied post-mitotic cell whose development and response to stress are associated with marked rearrangements of chromatin topology both in cis and in trans. I argue that RNA polymerase II clusters (i.e., transcription factories) and foci of the cardiac-specific splicing regulator RBM20 (i.e., splicing factories) exemplify the existence of trans-interacting chromatin domains (TIDs) with important roles in cellular homeostasis. Overall, I propose that inter-molecular 3D proximity between co-regulated nucleic acids may be a pervasive functional mechanism in biology.

Download Full-text

Protamine-DNA interaction

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100081863 ◽

1978 ◽

Vol 36 (2) ◽

pp. 200-201

Author(s):

D.P. Bazett-Jones ◽

F.P. Ottensmeyer

Keyword(s):

Small Volume ◽

Double Helix ◽

Dna Interaction ◽

Dark Field ◽

Sperm Head ◽

Nuclear Proteins ◽

Field Electron Microscopy ◽

Dark Field Electron ◽

Dna Double Helix ◽

Positively Charged

Dark field electron microscopy has been used for the study of the structure of individual macromolecules with a resolution to at least the 5Å level. The use of this technique has been extended to the investigation of structure of interacting molecules, particularly the interaction between DNA and fish protamine, a class of basic nuclear proteins of molecular weight 4,000 daltons.Protamine, which is synthesized during spermatogenesis, binds to chromatin, displaces the somatic histones and wraps up the DNA to fit into the small volume of the sperm head. It has been proposed that protamine, existing as an extended polypeptide, winds around the minor groove of the DNA double helix, with protamine's positively-charged arginines lining up with the negatively-charged phosphates of DNA. However, viewing protamine as an extended protein is inconsistent with the results obtained in our laboratory.

Download Full-text