scholarly journals A DNA Sequence Based Polymer Model for Chromatin Folding

2021 ◽  
Vol 22 (3) ◽  
pp. 1328
Author(s):  
Rui Zhou ◽  
Yi Qin Gao
Keyword(s):  
Dna Sequence ◽  
Cpg Island ◽  
Coarse Grained ◽  
Chromosome Territories ◽  
Base Pairs ◽  
Single Chromosome ◽  
Power Law Decay ◽  
Multiple Length Scales ◽  
Spatial Domains ◽  
Chromatin Folding

The recent development of sequencing technology and imaging methods has provided an unprecedented understanding of the inter-phase chromatin folding in mammalian nuclei. It was found that chromatin folds into topological-associated domains (TADs) of hundreds of kilo base pairs (kbps), and is further divided into spatially segregated compartments (A and B). The compartment B tends to be located near to the periphery or the nuclear center and interacts with other domains of compartments B, while compartment A tends to be located between compartment B and interacts inside the domains. These spatial domains are found to highly correlate with the mosaic CpG island (CGI) density. High CGI density corresponds to compartments A and small TADs, and vice versa. The variation of contact probability as a function of sequential distance roughly follows a power-law decay. Different chromosomes tend to segregate to occupy different chromosome territories. A model that can integrate these properties at multiple length scales and match many aspects is highly desired. Here, we report a DNA-sequence based coarse-grained block copolymer model that considers different interactions between blocks of different CGI density, interactions of TAD formation, as well as interactions between chromatin and the nuclear envelope. This model captures the various single-chromosome properties and partially reproduces the formation of chromosome territories.

scholarly journals A Multifactorial Signature of DNA Sequence and Polycomb Binding Predicts Aberrant CpG Island Methylation

2008 ◽  
Vol 69 (1) ◽  
pp. 282-291 ◽  
Author(s):  
Michael T. McCabe ◽  
Eva K. Lee ◽  
Paula M. Vertino
Keyword(s):  
Dna Sequence ◽  
Cpg Island ◽  
Cpg Island Methylation

scholarly journals Supercoiling DNA locates mismatches

2017 ◽  
Author(s):  
Andrew Dittmore ◽  
Sumitabha Brahmachari ◽  
Yasuhara Takagi ◽  
John F. Marko ◽  
Keir C. Neuman
Keyword(s):  
Dna Sequence ◽  
Base Pair ◽  
Dna Supercoiling ◽  
Magnetic Tweezers ◽  
Relative Probability ◽  
Base Pairs ◽  
Damage Sensing ◽  
Mismatched Base Pair ◽  
Monovalent Salt

We present a method of detecting sequence defects by supercoiling DNA with magnetic tweezers. The method is sensitive to a single mismatched base pair in a DNA sequence of several thousand base pairs. We systematically compare DNA molecules with 0 to 16 adjacent mismatches at 1 M monovalent salt and 3.5 pN force and show that, under these conditions, a single plectoneme forms and is stably pinned at the defect. We use these measurements to estimate the energy and degree of end-loop kinking at defects. From this, we calculate the relative probability of plectoneme pinning at the mismatch under physiologically relevant conditions. Based on this estimate, we propose that DNA supercoiling could contribute to mismatch and damage sensing in vivo.

Octamer and SPH motifs in the U1 enhancer cooperate to activate U1 RNA gene expression

1990 ◽  
Vol 10 (1) ◽  
pp. 341-352
Author(s):  
K A Roebuck ◽  
D P Szeto ◽  
K P Green ◽  
Q N Fan ◽  
W E Stumph
Keyword(s):  
Dna Sequence ◽  
Functional Activity ◽  
Stable Complex ◽  
Small Nuclear Rna ◽  
Base Pairs ◽  
Rna Transcription ◽  
Octamer Motif ◽  
Chicken Tissue ◽  
Nuclear Rna ◽  
Gc Box

The transcriptional enhancer of a chicken U1 small nuclear RNA gene has been shown to extend over approximately 50 base pairs of DNA sequence located 180 to 230 base pairs upstream of the U1 transcription initiation site. It is composed of multiple functional motifs, including a GC box, an octamer motif, and a novel SPH motif. The contributions of these three distinct sequence motifs to enhancer function were studied with an oocyte expression assay. Under noncompetitive conditions in oocytes, the SPH motif is capable of stimulating U1 RNA transcription in the absence of the other functional motifs, whereas the octamer motif by itself lacks this ability. However, to form a transcription complex that is stable to challenge by a second competing small nuclear RNA transcription unit, both the octamer and SPH motifs are required. The GC box, although required for full enhancer activity, is not essential for stable complex formation in oocytes. Site-directed mutagenesis was used to study the DNA sequence requirements of the SPH motif. Functional activity of the SPH motif is spread throughout a 24-base-pair region 3' of the octamer but is particularly dependent upon sequences near an SphI restriction site located at the center of the SPH motif. Using embryonic chicken tissue as a source material, we identified and partially purified a factor, termed SBF, that binds sequence specifically to the SPH motif of the U1 enhancer. The ability of this factor to recognize and bind to mutant enhancer DNA fragments in vitro correlates with the functional activity of the corresponding enhancer sequences in vivo.

A new species of big-headed, fanged dicroglossine frog (Genus Limnonectes) from Thailand

Zootaxa ◽  
2008 ◽  
Vol 1807 (1) ◽  
pp. 26 ◽  
Author(s):  
DAVID S. McLEOD
Keyword(s):  
New Species ◽  
Dna Sequence ◽  
Sequence Data ◽  
Sequence Divergence ◽  
Type Material ◽  
Base Pairs ◽  
Dna Sequence Data ◽  
16S Gene ◽  
A New Species

A new species of the dicroglossine genus Limnonectes from eastern Thailand and its tadpole are described. Analysis of DNA sequence data from 2518 base-pairs of the mitochondrial 12S and 16S gene regions places the species within the complex of frogs currently referred to as Limnonectes kuhlii and demonstrates it to be a separate lineage (>18% sequence divergence from type-material of L. kuhlii from Java). The new species differs from L. kuhlii by having nuptial pads, a greater snout–vent length, and different relative finger lengths than specimens from Java. It has more extensive toe webbing, a different arrangement of nuptial pads, and a greater snout–vent length than Limnonectes laticeps. The new species, which lacks vocal slits, also can be distinguished from the morphologically similar Limnonectes namiyei from Japan, which possesses vocal slits.

scholarly journals CpG Island Methylation in Human Lymphocytes Is Highly Correlated with DNA Sequence, Repeats, and Predicted DNA Structure

PLoS Genetics ◽  
2006 ◽  
Vol 2 (3) ◽  
pp. e26 ◽  
Author(s):  
Christoph Bock ◽  
Martina Paulsen ◽  
Sascha Tierling ◽  
Thomas Mikeska ◽  
Thomas Lengauer ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Cpg Island ◽  
Human Lymphocytes ◽  
Dna Structure ◽  
Cpg Island Methylation ◽  
Highly Correlated ◽  
Dna Sequence Repeats

4D Graphical representation research of DNA sequences

2015 ◽  
Vol 08 (01) ◽  
pp. 1550004 ◽  
Author(s):  
Chengjie Tan ◽  
Shanshan Li ◽  
Ping Zhu
Keyword(s):  
Dna Sequence ◽  
Dna Sequences ◽  
Graphical Representation ◽  
Hierarchical Cluster ◽  
Positive Outcome ◽  
Biological Information ◽  
Terminal Point ◽  
Base Pairs ◽  
Representation Method ◽  
The Times

Graphical representation of DNA sequences is a key component in studying biological problems. In order to gain new insights in DNA sequences, this paper combined the digitized methods of single-base, base pairs and coding in triplet bases with the times of base appearing, and then a novel 4D graphical representation method of DNA sequences was put forward. It was a one-to-one correspondence of the arbitrary DNA sequence and 4D graphical representation, that avoided causing non-unique 4D graphical representation and overlapping lines. The method could reflect the biological information features of DNA sequence more comprehensively and effectively without any losses. Based on the 4D graphical representation, we used the geometric center of 4D graphical representation as eigenvalue of DNA sequences analyses, which kept the original features of the data, and then established the Euclidean distances and included angles between vectors' terminal point for similarity analyses of the first extron of the beta-globulin gene among 11 species. Finally, we established the graph of systematic hierarchical cluster analysis of 11 species to observe more easily the relationship between species. A positive outcome was reached, and the results were in accord with biological taxonomy, which also supported the rationality and effectiveness of the novel 4D graphical representation.

scholarly journals G-Dash: A Genome Dashboard Integrating Modeling and Informatics

2018 ◽  
Author(s):  
Zilong Li ◽  
Ran Sun ◽  
Thomas C Bishop
Keyword(s):  
Significant Variation ◽  
Genome Browser ◽  
Coarse Grained ◽  
Base Pairs ◽  
Web Based ◽  
Coarse Grained Model ◽  
A Genome ◽  
Sample Application ◽  
Material Studies ◽  
Chromatin Modeling

Genomics is a sequence based informatics science and a structure based molecular material science. There are few tools available that unite these approaches in a scientifically robust manner. Here we describe G-Dash, a web based prototype of a genomics dashboard, specifically designed to integrate informatics and 4D material studies of chromatin. G-Dash unites our Interactive Chromatin Modeling(ICM) tools with the Biodalliance genome browser and the JSMol molecular viewer to rapidly fold any DNA sequence into atomic or coarse-grained models of DNA, nucleosomes or chromatin. As a chromatin modeling tool, G-Dash enables users to specify nucleosome positions from various experimental or theoretical sources, interactively manipulate nucleosomes, and assign different conformational states to each nucleosome. As an informatics tool, data associated with 3D structures are displayed as tracks in a genome browser. The exchange of data between informatics and structure is bi-directional so any informatics track can inform a molecular structure (e.g. color by function) and structure features can be displayed as informatics tracks in a genome browser(e.g. Roll, Slide, or Twist). As a sample application, models of the CHA1 promoter based on experimentally determined nucleosome positions are explored with G-Dash. Steric clashes and DNA knotting are observed but can be resolved with G-Dash's minimal coarse-grained model without significant variation in structure. Results raise questions about the interpretation of nucleosome positioning data and promoter structures. In this regard, G-Dash is a novel tool for investigating structure-function relationships for regions of the genome ranging from base pairs to chromosomes and for generating, validating and testing mechanistic hypotheses.

scholarly journals Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations

2017 ◽  
Author(s):  
Toru Niina ◽  
Giovanni B. Brandani ◽  
Cheng Tan ◽  
Shoji Takada
Keyword(s):  
Hydrogen Bond ◽  
Dna Sequence ◽  
Base Pair ◽  
Sliding Mode ◽  
Nucleosome Positioning ◽  
Eukaryotic Genome ◽  
Coarse Grained ◽  
Histone Octamer ◽  
Hydrogen Bond Interactions ◽  
Nucleosome Sliding

AbstractWhile nucleosome positioning on eukaryotic genome play important roles for genetic regulation, molecular mechanisms of nucleosome positioning and sliding along DNA are not well understood. Here we investigated thermally-activated spontaneous nucleosome sliding mechanisms developing and applying a coarse-grained molecular simulation method that incorporates both long-range electrostatic and short-range hydrogen-bond interactions between histone octamer and DNA. The simulations revealed two distinct sliding modes depending on the nucleosomal DNA sequence. A uniform DNA sequence showed frequent sliding with one base pair step in a rotation-coupled manner, akin to screw-like motions. On the contrary, a strong positioning sequence, the so-called 601 sequence, exhibits rare, abrupt transitions of five and ten base pair steps without rotation. Moreover, we evaluated the importance of hydrogen bond interactions on the sliding mode, finding that strong and weak bonds favor respectively the rotation-coupled and -uncoupled sliding movements.Author summaryNucleosomes are fundamental units of chromatin folding consisting of double-stranded DNA wrapped ∼1.7 times around a histone octamer. By densely populating the eukaryotic genome, nucleosomes enable efficient genome compaction inside the cellular nucleus. However, the portion of DNA occupied by a nucleosome can hardly be accessed by other DNA-binding proteins, obstructing fundamental cellular processes such as DNA replication and transcription. DNA compaction and access by other proteins can simultaneously be achieved via the dynamical repositioning of nucleosomes, which can slide along the DNA sequence. In this study, we developed and used coarse-grained molecular dynamics simulations to reveal the molecular details of nucleosome sliding. We find that the sliding mode is highly dependent on the underlying DNA sequence. Specifically, a sequence with a strong nucleosome positioning signal slides via large jumps by five and ten base pairs, preserving the optimal DNA bending profile. On the other hand, uniform sequences without the positioning signal slide via a screw-like motion of DNA, one base pair at the time. These results show that sequence has a large effect not only on the formation of nucleosomes, but also on the kinetics of repositioning.

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