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https://www.readbyqxmd.com/read/29149895/novel-insights-into-chromosomal-conformations-in-cancer
#1
REVIEW
Ruobing Jia, Peiwei Chai, He Zhang, Xianqun Fan
Exploring gene function is critical for understanding the complexity of life. DNA sequences and the three-dimensional organization of chromatin (chromosomal interactions) are considered enigmatic factors underlying gene function, and interactions between two distant fragments can regulate transactivation activity via mediator proteins. Thus, a series of chromosome conformation capture techniques have been developed, including chromosome conformation capture (3C), circular chromosome conformation capture (4C), chromosome conformation capture carbon copy (5C), and high-resolution chromosome conformation capture (Hi-C)...
November 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29149597/structural-basis-for-shelterin-bridge-assembly
#2
Jin-Kwang Kim, Jinqiang Liu, Xichan Hu, Clinton Yu, Kyle Roskamp, Banumathi Sankaran, Lan Huang, Elizabeth A Komives, Feng Qiao
Telomere elongation through telomerase enables chromosome survival during cellular proliferation. The conserved multifunctional shelterin complex associates with telomeres to coordinate multiple telomere activities, including telomere elongation by telomerase. Similar to the human shelterin, fission yeast shelterin is composed of telomeric sequence-specific double- and single-stranded DNA-binding proteins, Taz1 and Pot1, respectively, bridged by Rap1, Poz1, and Tpz1. Here, we report the crystal structure of the fission yeast Tpz1(475-508)-Poz1-Rap1(467-496) complex that provides the structural basis for shelterin bridge assembly...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149264/sim3c-simulation-of-hi-c-and-meta3c-proximity-ligation-sequencing-technologies
#3
Matthew Z DeMaere, Aaron E Darling
Background: Chromosome conformation capture (3C) and Hi-C DNA sequencing methods have rapidly advanced our understanding of the spatial organization of genomes and metagenomes. Many variants of these protocols have been developed, each with their own strengths. Currently there is no systematic means for simulating sequence data from this family of sequencing protocols, potentially hindering the advancement of algorithms to exploit this new datatype. Findings: We describe a computational simulator that, given simple parameters and reference genome sequences, will simulate Hi-C sequencing on those sequences...
November 15, 2017: GigaScience
https://www.readbyqxmd.com/read/29149036/identification-of-the-caprine-keratin-associated-protein-20-2-kap20-2-gene-and-its-effect-on-cashmere-traits
#4
Jiqing Wang, Longjie Che, Jon G H Hickford, Huitong Zhou, Zhiyun Hao, Yuzhu Luo, Jiang Hu, Xiu Liu, Shaobin Li
The gene encoding the high glycine/tyrosine keratin-associated protein 20-2 (KAP20-2) gene has been described in humans, but has not been identified in any livestock species. A search for similar sequences in the caprine genome using the human KAP20-2 gene (KRTAP20-2) revealed a homologous sequence on chromosome 1. Three different banding patterns representing distinct sequences (A-C) in Longdong cashmere goats were identified using polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis...
November 17, 2017: Genes
https://www.readbyqxmd.com/read/29137603/clustertad-an-unsupervised-machine-learning-approach-to-detecting-topologically-associated-domains-of-chromosomes-from-hi-c-data
#5
Oluwatosin Oluwadare, Jianlin Cheng
BACKGROUND: With the development of chromosomal conformation capturing techniques, particularly, the Hi-C technique, the study of the spatial conformation of a genome is becoming an important topic in bioinformatics and computational biology. The Hi-C technique can generate genome-wide chromosomal interaction (contact) data, which can be used to investigate the higher-level organization of chromosomes, such as Topologically Associated Domains (TAD), i.e., locally packed chromosome regions bounded together by intra chromosomal contacts...
November 14, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29128709/integrating-experiment-theory-and-simulation-to-determine-the-structure-and-dynamics-of-mammalian-chromosomes
#6
REVIEW
G Tiana, L Giorgetti
Eukaryotic chromosomes are complex polymers, which largely exceed in size most biomolecules that are usually modelled in computational studies and whose molecular interactions are to a large extent unknown. Since the folding of the chromatin fiber in the cell nucleus is tightly linked to biological function and gene expression in particular, characterizing the conformational and dynamical properties of chromosomes has become crucial in order to better understand how genes are regulated. In parallel with the development of experimental techniques allowing to measure physical contacts within chromosomes inside the cell nucleus, a large variety of physical models to study the structure and mechanisms of chromosome folding have recently emerged...
November 8, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29121981/intrinsic-dna-curvature-in-trypanosomes
#7
Pablo Smircich, Najib M El-Sayed, Beatriz Garat
BACKGROUND: Trypanosoma cruzi and Trypanosoma brucei are protozoan parasites causing Chagas disease and African sleeping sickness, displaying unique features of cellular and molecular biology. Remarkably, no canonical signals for RNA polymerase II promoters, which drive protein coding genes transcription, have been identified so far. The secondary structure of DNA has long been recognized as a signal in biological processes and more recently, its involvement in transcription initiation in Leishmania was proposed...
November 9, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29115939/genome-wide-association-studies-and-genomic-prediction-of-breeding-values-for-calving-performance-and-body-conformation-traits-in-holstein-cattle
#8
Mohammed K Abo-Ismail, Luiz F Brito, Stephen P Miller, Mehdi Sargolzaei, Daniela A Grossi, Steve S Moore, Graham Plastow, Paul Stothard, Shadi Nayeri, Flavio S Schenkel
BACKGROUND: Our aim was to identify genomic regions via genome-wide association studies (GWAS) to improve the predictability of genetic merit in Holsteins for 10 calving and 28 body conformation traits. Animals were genotyped using the Illumina Bovine 50 K BeadChip and imputed to the Illumina BovineHD BeadChip (HD). GWAS were performed on 601,717 real and imputed single nucleotide polymorphism (SNP) genotypes using a single-SNP mixed linear model on 4841 Holstein bulls with breeding value predictions and followed by gene identification and in silico functional analyses...
November 7, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/29098179/dna-topology-in-chromatin-is-defined-by-nucleosome-spacing
#9
Tatiana Nikitina, Davood Norouzi, Sergei A Grigoryev, Victor B Zhurkin
In eukaryotic nucleosomes, DNA makes ~1.7 superhelical turns around histone octamer. However, there is a long-standing discrepancy between the nucleosome core structure determined by x-ray crystallography and measurements of DNA topology in circular minichromosomes, indicating that there is only ~1.0 superhelical turn per nucleosome. Although several theoretical assumptions were put forward to explain this paradox by conformational variability of the nucleosome linker, none was tested experimentally. We analyzed topological properties of DNA in circular nucleosome arrays with precisely positioned nucleosomes...
October 2017: Science Advances
https://www.readbyqxmd.com/read/29094699/two-independent-modes-of-chromatin-organization-revealed-by-cohesin-removal
#10
Wibke Schwarzer, Nezar Abdennur, Anton Goloborodko, Aleksandra Pekowska, Geoffrey Fudenberg, Yann Loe-Mie, Nuno A Fonseca, Wolfgang Huber, Christian H Haering, Leonid Mirny, Francois Spitz
Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes...
November 2, 2017: Nature
https://www.readbyqxmd.com/read/29093029/chromatin-conformation-links-distal-target-genes-to-ckd-loci
#11
Maarten M Brandt, Claartje A Meddens, Laura Louzao-Martinez, Noortje A M van den Dungen, Nico R Lansu, Edward E S Nieuwenhuis, Dirk J Duncker, Marianne C Verhaar, Jaap A Joles, Michal Mokry, Caroline Cheng
Genome-wide association studies (GWASs) have identified many genetic risk factors for CKD. However, linking common variants to genes that are causal for CKD etiology remains challenging. By adapting self-transcribing active regulatory region sequencing, we evaluated the effect of genetic variation on DNA regulatory elements (DREs). Variants in linkage with the CKD-associated single-nucleotide polymorphism rs11959928 were shown to affect DRE function, illustrating that genes regulated by DREs colocalizing with CKD-associated variation can be dysregulated and therefore, considered as CKD candidate genes...
November 1, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29091999/evaluation-and-comparison-of-methods-for-recapitulation-of-3d-spatial-chromatin-structures
#12
Jincheol Park, Shili Lin
How chromosomes fold and how distal genomic elements interact with one another at a genomic scale have been actively pursued in the past decade following the seminal work describing the Chromosome Conformation Capture (3C) assay. Essentially, 3C-based technologies produce two-dimensional (2D) contact maps that capture interactions between genomic fragments. Accordingly, a plethora of analytical methods have been proposed to take a 2D contact map as input to recapitulate the underlying whole genome three-dimensional (3D) structure of the chromatin...
October 30, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29080874/-computer-methods-of-analysis-of-chromosome-contacts-in-the-cell-nucleus-based-on-sequencing-technology-data
#13
Y L Orlov, O Thierry, A G Bogomolov, A V Tsukanov, E V Kulakova, E R Galieva, A O Bragin, G Li
The study spatial chromosome structure and chromosome folding in the interphase cell nucleus is an important challenge of world science. Detection of eukaryotic genome regions that physically interact with each other could be done by modern sequencing technologies. A basic method of chromosome folding by total sequencing of contacting DNA fragments is HI-C. Long-range chromosomal interactions play an important role in gene transcription and regulation. The study of chromosome interactions, 3D (three-dimensional) genome structure and its effect on gene transcription allows revealing fundamental biological processes from a viewpoint of structural regulation and are important for cancer research...
October 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/29076094/chromosome-conformation-capture-3c-and-higher-with-erythroid-samples
#14
Ivan Krivega, Ann Dean
Chromosome conformation capture (3C) allows for the determination of the proximity in nuclei of DNA sequences that are linearly distant from one another in the genome. Proximity that is above that expected from random interaction provides evidence for potential long-range functional interactions such as between enhancers and their target genes. Many controls are required to convincingly demonstrate increased frequency of interaction between sequences and stringent functional tests must also be applied. Here, we present methodology suitable for 3C experiments that can also be applied as the basis for related 4C, 5C, and Hi-C approaches...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29068057/exploring-the-influence-of-hyperthermophilic-protein-ssh10b-on-the-stability-and-conformation-of-rna-by-molecular-dynamics-simulation
#15
Xue Zhang, Qing-Chuan Zheng
The hyperthermophilic Ssh10b from Sulfolobus shibatae is a member of the Sac10b family, which binds RNA in vivo as a physiological substrate, and it has been postulated to play a key role in chromosomal organization in Archaea. Even though the crystal structure of Ssh10b-RNA was resolved successively by X-ray diffraction (Protein Data Bank [PDB] code: 3WBM), the detailed dynamic characteristics of Ssh10b-RNA are still unclear. In this study, molecular dynamics (MDs) simulations at 6 temperatures (300, 350, 375, 400, 450, and 500 K) and molecular mechanics Generalized-Born surface area (MM-GB/SA) free energy calculations were performed to investigate the mechanism of how Ssh10b protects and stabilizes RNA...
October 25, 2017: Biopolymers
https://www.readbyqxmd.com/read/29057826/potential-role-of-phase-separation-of-repetitive-dna-in-chromosomal-organization
#16
Shao-Jun Tang
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...
October 18, 2017: Genes
https://www.readbyqxmd.com/read/29053968/multiscale-3d-genome-rewiring-during-mouse-neural-development
#17
Boyan Bonev, Netta Mendelson Cohen, Quentin Szabo, Lauriane Fritsch, Giorgio L Papadopoulos, Yaniv Lubling, Xiaole Xu, Xiaodan Lv, Jean-Philippe Hugnot, Amos Tanay, Giacomo Cavalli
Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29052196/3c-in-maize-and-arabidopsis
#18
Blaise Weber, Suraj Jamge, Maike Stam
With Chromosome Conformation Capture (3C), the relative interaction frequency of one chromosomal fragment with another can be determined. The technique is especially suited for unraveling the 3D organization of specific loci when focusing on aspects such as enhancer-promoter interactions or other topological conformations of the genome. 3C has been extensively used in animal systems, among others providing insight into gene regulation by distant cis-regulatory elements. In recent years, the 3C technique has been applied in plant research...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29052195/technical-review-a-hitchhiker-s-guide-to-chromosome-conformation-capture
#19
Stefan Grob, Giacomo Cavalli
The introduction of chromosome conformation capture (3C) technologies boosted the field of 3D-genome research and significantly enhanced the available toolset to study chromosomal architecture. 3C technologies not only offer increased resolution compared to the previously dominant cytological approaches but also allow the simultaneous study of genome-wide 3D chromatin contacts, thereby enabling a candidate-free perspective on 3D-genome architecture. Since its introduction in 2002, 3C technologies evolved rapidly and now constitute a collection of tools, each with their strengths and pitfalls with respect to specific research questions...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29052194/unraveling-the-complex-epigenetic-mechanisms-that-regulate-gene-activity
#20
Marian Bemer
Our understanding of the epigenetic mechanisms that regulate gene expression has been largely increased in recent years by the development and refinement of different techniques. This has revealed that gene transcription is highly influenced by epigenetic mechanisms, i.e., those that do not involve changes in the genome sequence, but rather in nuclear architecture, chromosome conformation and histone and DNA modifications. Our understanding of how these different levels of epigenetic regulation interact with each other and with classical transcription-factor based gene regulation to influence gene transcription has just started to emerge...
2018: Methods in Molecular Biology
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