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https://www.readbyqxmd.com/read/28435001/hi-c-2-0-an-optimized-hi-c-procedure-for-high-resolution-genome-wide-mapping-of-chromosome-conformation
#1
Houda Belaghzal, Job Dekker, Johan H Gibcus
Chromosome conformation capture-based methods such as Hi-C have become mainstream techniques for the study of the 3D organization of genomes. These methods convert chromatin interactions reflecting topological chromatin structures into digital information (counts of pair-wise interactions). Here, we describe an updated protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single protocol for efficient and high-resolution capture of chromatin interactions. This protocol combines chromatin digestion and frequently cutting enzymes to obtain kilobase (Kb) resolution...
April 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28432015/blatm-2-0-a-genetic-tool-revealing-preferred-antiparallel-interaction-of-transmembrane-helix-4-of-the-dual-topology-protein-emre
#2
Ayse Julius, Lisa Laur, Christoph Schanzenbach, Dieter Langosch
Parallel and antiparallel transmembrane helix-helix interactions support the folding and non-covalent assembly of many integral membrane proteins. While several genetic tools are currently in use to study parallel transmembrane helix-helix interactions, antiparallel associations have been difficult to determine. Here, we present a novel genetic approach, termed BLaTM 2.0, which can be used in combination with the recently presented BLaTM 1.2 to compare the efficiency of antiparallel and parallel TMD interactions in a natural membrane...
April 18, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28424523/cohesin-is-positioned-in-mammalian-genomes-by-transcription-ctcf-and-wapl
#3
Georg A Busslinger, Roman R Stocsits, Petra van der Lelij, Elin Axelsson, Antonio Tedeschi, Niels Galjart, Jan-Michael Peters
Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-range chromosomal cis-interactions. Cohesin is also present at these sites, but has been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites, according to this or other models, is unknown...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28424353/constrained-release-of-lamina-associated-enhancers-and-genes-from-the-nuclear-envelope-during-t-cell-activation-facilitates-their-association-in-chromosome-compartments
#4
Michael I Robson, Jose I de Las Heras, Rafal Czapiewski, Aishwarya Sivakumar, Alastair R W Kerr, Eric Schirmer
The 3D organization of the genome changes concomitantly with expression changes during hematopoiesis and immune activation. Studies have focused either on lamina-associated domains (LADs) or on topologically-associated domains (TADs), defined by preferential local chromatin interactions, and chromosome compartments, defined as higher-order interactions between TADs sharing functionally similar states. However, few studies have investigated how these affect one another. To address this, we mapped LADs using Lamin B1-DamID during Jurkat T-cell activation, finding significant genome re-organization at the nuclear periphery dominated by release of loci frequently important for T-cell function...
April 19, 2017: Genome Research
https://www.readbyqxmd.com/read/28424341/alterations-in-three-dimensional-organization-of-the-cancer-genome-and-epigenome
#5
Joanna Achinger-Kawecka, Phillippa C Taberlay, Susan J Clark
The structural and functional basis of the genome is provided by the three-dimensional (3D) chromatin state. To enable accurate gene regulation, enhancer elements and promoter regions are brought into close spatial proximity to ensure proper, cell type-specific gene expression. In cancer, genetic and epigenetic processes can deregulate the transcriptional program. To investigate whether the 3D chromatin state is also disrupted in cancer we performed Hi-C chromosome conformation sequencing in normal and prostate cancer cells and compared the chromatin interaction maps with changes to the genome and epigenome...
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28420341/genetic-sequence-based-prediction-of-long-range-chromatin-interactions-suggests-a-potential-role-of-short-tandem-repeat-sequences-in-genome-organization
#6
Sarvesh Nikumbh, Nico Pfeifer
BACKGROUND: Knowing the three-dimensional (3D) structure of the chromatin is important for obtaining a complete picture of the regulatory landscape. Changes in the 3D structure have been implicated in diseases. While there exist approaches that attempt to predict the long-range chromatin interactions, they focus only on interactions between specific genomic regions - the promoters and enhancers, neglecting other possibilities, for instance, the so-called structural interactions involving intervening chromatin...
April 18, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28408976/when-tads-go-bad-chromatin-structure-and-nuclear-organisation-in-human-disease
#7
REVIEW
Vera B Kaiser, Colin A Semple
Chromatin in the interphase nucleus is organised as a hierarchical series of structural domains, including self-interacting domains called topologically associating domains (TADs). This arrangement is thought to bring enhancers into closer physical proximity with their target genes, which often are located hundreds of kilobases away in linear genomic distance. TADs are demarcated by boundary regions bound by architectural proteins, such as CTCF and cohesin, although much remains to be discovered about the structure and function of these domains...
2017: F1000Research
https://www.readbyqxmd.com/read/28388407/chromatin-architecture-emerges-during-zygotic-genome-activation-independent-of-transcription
#8
Clemens B Hug, Alexis G Grimaldi, Kai Kruse, Juan M Vaquerizas
Chromatin architecture is fundamental in regulating gene expression. To investigate when spatial genome organization is first established during development, we examined chromatin conformation during Drosophila embryogenesis and observed the emergence of chromatin architecture within a tight time window that coincides with the onset of transcription activation in the zygote. Prior to zygotic genome activation, the genome is mostly unstructured. Early expressed genes serve as nucleation sites for topologically associating domain (TAD) boundaries...
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28369605/yeast-sub1-and-human-pc4-are-g-quadruplex-binding-proteins-that-suppress-genome-instability-at-co-transcriptionally-formed-g4-dna
#9
Christopher R Lopez, Shivani Singh, Shashank Hambarde, Wezley C Griffin, Jun Gao, Shubeena Chib, Yang Yu, Grzegorz Ira, Kevin D Raney, Nayun Kim
G-quadruplex or G4 DNA is a non-B secondary DNA structure consisting of a stacked array of guanine-quartets that can disrupt critical cellular functions such as replication and transcription. When sequences that can adopt Non-B structures including G4 DNA are located within actively transcribed genes, the reshaping of DNA topology necessary for transcription process stimulates secondary structure-formation thereby amplifying the potential for genome instability. Using a reporter assay designed to study G4-induced recombination in the context of an actively transcribed locus in Saccharomyces cerevisiae, we tested whether co-transcriptional activator Sub1, recently identified as a G4-binding factor, contributes to genome maintenance at G4-forming sequences...
March 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28369076/transient-chromatin-properties-revealed-by-polymer-models-and-stochastic-simulations-constructed-from-chromosomal-capture-data
#10
Ofir Shukron, David Holcman
Chromatin organization can be probed by Chromosomal Capture (5C) data, from which the encounter probability (EP) between genomic sites is presented in a large matrix. This matrix is averaged over a large cell population, revealing diagonal blocks called Topological Associating Domains (TADs) that represent a sub-chromatin organization. To study the relation between chromatin organization and gene regulation, we introduce a computational procedure to construct a bead-spring polymer model based on the EP matrix...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28368814/predicting-protein-functions-by-using-unbalanced-random-walk-algorithm-on-three-biological-networks
#11
Wei Peng, Min Li, Lu Chen, Lusheng Wang
With the gap between the sequence data and their functional annotations becomes increasing wider, many computational methods have been proposed to annotate functions for unknown proteins. However, designing effective methods to make good use of various biological resources is still a big challenge for researchers due to function diversity of proteins. In this work, we propose a new method named ThrRW, which takes several steps of random walking on three different biological networks: protein interaction network (PIN), domain co-occurrence network (DCN), and functional interrelationship network (FIN), respectively, so as to infer functional information from neighbors in the corresponding networks...
March 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28359583/enhancer-derived-lncrnas-regulate-genome-architecture-fact-or-fiction
#12
Stephanie Fanucchi, Musa M Mhlanga
How does the non-coding portion of the genome contribute to the regulation of genome architecture? A recent paper by Tan et al. focuses on the relationship between cis-acting complex-trait-associated lincRNAs and the formation of chromosomal contacts in topologically associating domains (TADs).
March 27, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28355537/ephemeral-protein-binding-to-dna-shapes-stable-nuclear-bodies-and-chromatin-domains
#13
Chris A Brackley, Benno Liebchen, Davide Michieletto, Francois Mouvet, Peter R Cook, Davide Marenduzzo
Fluorescence microscopy reveals that the contents of many (membrane-free) nuclear bodies exchange rapidly with the soluble pool while the underlying structure persists; such observations await a satisfactory biophysical explanation. To shed light on this, we perform large-scale Brownian dynamics simulations of a chromatin fiber interacting with an ensemble of (multivalent) DNA-binding proteins able to switch between an "on" (binding) and an "off" (nonbinding) state. This system provides a model for any DNA-binding protein that can be posttranslationally modified to change its affinity for DNA (e...
March 28, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28355183/single-nucleus-hi-c-reveals-unique-chromatin-reorganization-at-oocyte-to-zygote-transition
#14
Ilya M Flyamer, Johanna Gassler, Maxim Imakaev, Hugo B Brandão, Sergey V Ulianov, Nezar Abdennur, Sergey V Razin, Leonid A Mirny, Kikuë Tachibana-Konwalski
Chromatin is reprogrammed after fertilization to produce a totipotent zygote with the potential to generate a new organism. The maternal genome inherited from the oocyte and the paternal genome provided by sperm coexist as separate haploid nuclei in the zygote. How these two epigenetically distinct genomes are spatially organized is poorly understood. Existing chromosome conformation capture-based methods are not applicable to oocytes and zygotes owing to a paucity of material. To study three-dimensional chromatin organization in rare cell types, we developed a single-nucleus Hi-C (high-resolution chromosome conformation capture) protocol that provides greater than tenfold more contacts per cell than the previous method...
April 6, 2017: Nature
https://www.readbyqxmd.com/read/28348222/form-and-function-of-topologically-associating-genomic-domains-in-budding-yeast
#15
Umut Eser, Devon Chandler-Brown, Ferhat Ay, Aaron F Straight, Zhijun Duan, William Stafford Noble, Jan M Skotheim
The genome of metazoan cells is organized into topologically associating domains (TADs) that have similar histone modifications, transcription level, and DNA replication timing. Although similar structures appear to be conserved in fission yeast, computational modeling and analysis of high-throughput chromosome conformation capture (Hi-C) data have been used to argue that the small, highly constrained budding yeast chromosomes could not have these structures. In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28342236/resolving-protein-structure-function-binding-site-relationships-from-a-binding-site-similarity-network-perspective
#16
Richa Mudgal, Narayanaswamy Srinivasan, Nagasuma Chandra
Functional annotation is seldom straightforward with complexities arising due to functional divergence in protein families or functional convergence between non-homologous protein families, leading to mis-annotations. An enzyme may contain multiple domains and not all domains may be involved in a given function, adding to the complexity in function annotation. To address this, we use binding site information from bound cognate ligands and catalytic residues, since it can help in resolving fold-function relationships at a finer level and with higher confidence...
March 25, 2017: Proteins
https://www.readbyqxmd.com/read/28334818/chromosomal-dynamics-predicted-by-an-elastic-network-model-explains-genome-wide-accessibility-and-long-range-couplings
#17
Natalie Sauerwald, She Zhang, Carl Kingsford, Ivet Bahar
Understanding the three-dimensional (3D) architecture of chromatin and its relation to gene expression and regulation is fundamental to understanding how the genome functions. Advances in Hi-C technology now permit us to study 3D genome organization, but we still lack an understanding of the structural dynamics of chromosomes. The dynamic couplings between regions separated by large genomic distances (>50 Mb) have yet to be characterized. We adapted a well-established protein-modeling framework, the Gaussian Network Model (GNM), to model chromatin dynamics using Hi-C data...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334773/a-critical-assessment-of-topologically-associating-domain-prediction-tools
#18
Rola Dali, Mathieu Blanchette
Topologically associating domains (TADs) have been proposed to be the basic unit of chromosome folding and have been shown to play key roles in genome organization and gene regulation. Several different tools are available for TAD prediction, but their properties have never been thoroughly assessed. In this manuscript, we compare the output of seven different TAD prediction tools on two published Hi-C data sets. TAD predictions varied greatly between tools in number, size distribution and other biological properties...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28323041/quantitative-analyses-of-the-3d-nuclear-landscape-recorded-with-super-resolved-fluorescence-microscopy
#19
Volker J Schmid, Marion Cremer, Thomas Cremer
Recent advancements of super-resolved fluorescence microscopy have revolutionized microscopic studies of cells, including the exceedingly complex structural organization of cell nuclei in space and time. In this paper we describe and discuss tools for (semi-) automated, quantitative 3D analyses of the spatial nuclear organization. These tools allow the quantitative assessment of highly resolved different chromatin compaction levels in individual cell nuclei, which reflect functionally different regions or sub-compartments of the 3D nuclear landscape, and measurements of absolute distances between sites of different chromatin compaction...
March 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28315770/biophysics-and-protein-corona-analysis-of-janus-cyclodextrin-dna-nanocomplexes-efficient-cellular-transfection-on-cancer-cells
#20
M Martínez-Negro, G Caracciolo, S Palchetti, D Pozzi, A L Capriotti, C Cavaliere, A Laganà, C Ortiz Mellet, J M Benito, J M García Fernández, E Aicart, E Junquera
The self-assembling processes underlining the capabilities of facially differentiated ("Janus") polycationic amphiphilic cyclodextrins (paCDs) as non-viral gene nanocarriers have been investigated by a pluridisciplinary approach. Three representative Janus paCDs bearing a common tetradecahexanoyl multitail domain at the secondary face and differing in the topology of the cluster of amino groups at the primary side were selected for this study. All of them compact pEGFP-C3 plasmid DNA and promote transfection in HeLa and MCF-7 cells, both in absence and in presence of human serum...
March 15, 2017: Biochimica et Biophysica Acta
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