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chromosome conformation capture

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https://www.readbyqxmd.com/read/28230735/new-evidence-for-the-theory-of-chromosome-organization-by-repetitive-elements-core
#1
Shao-Jun Tang
Repetitive DNA elements were proposed to coordinate chromatin folding and interaction in chromosomes by their intrinsic homology-based clustering ability. A recent analysis of the data sets from chromosome-conformation-capture experiments confirms the spatial clustering of DNA repeats of the same family in the nuclear space, and thus provides strong new support for the CORE theory.
February 20, 2017: Genes
https://www.readbyqxmd.com/read/28174238/functional-characterisation-of-cis-regulatory-elements-governing-dynamic-eomes-expression-in-the-early-mouse-embryo
#2
Claire S Simon, Damien J Downes, Matthew E Gosden, Jelena Telenius, Douglas R Higgs, Jim R Hughes, Ita Costello, Elizabeth K Bikoff, Elizabeth J Robertson
The T-box transcription factor (TF) Eomes is a key regulator of cell fate decisions during early mouse development. The cis-acting regulatory elements that direct expression in the anterior visceral endoderm (AVE), primitive streak (PS) and definitive endoderm (DE) have yet to be defined. Here, we identified three gene-proximal enhancer-like sequences (PSE_a, PSE_b and VPE) that faithfully activate tissue specific expression in transgenic embryos. However, targeted deletion experiments demonstrate that PSE_a and PSE_b are dispensable and only the VPE is required for optimal Eomes expression in vivo Embryos lacking this enhancer display variably penetrant defects in anterior-posterior axis orientation and DE formation...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28161540/genome-organization-in-the-nucleus-from-dynamic-measurements-to-a-functional-model
#3
REVIEW
Anat Vivante, Eugene Brozgol, Irena Bronshtein, Yuval Garini
A biological system is by definition a dynamic environment encompassing kinetic processes that occur at different length scales and time ranges. To explore this type of system, spatial information needs to be acquired at different time scales. This means overcoming significant hurdles, including the need for stable and precise labeling of the required probes and the use of state of the art optical methods. However, to interpret the acquired data, biophysical models that can account for these biological mechanisms need to be developed...
February 1, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28159771/improving-and-correcting-the-contiguity-of-long-read-genome-assemblies-of-three-plant-species-using-optical-mapping-and-chromosome-conformation-capture-data
#4
Wen-Biao Jiao, Gonzalo Garcia Accinelli, Benjamin Hartwig, Christiane Kiefer, David Baker, Edouard Severing, Eva-Maria Willing, Mathieu Piednoel, Stefan Woetzel, Eva Madrid-Herrero, Bruno Huettel, Ulrike Hümann, Richard Reinhard, Marcus A Koch, Daniel Swan, Bernardo Clavijo, George Coupland, Korbinian Schneeberger
Long-read sequencing can overcome the weaknesses of short reads in the assembly of eukaryotic genomes, however, at present additional scaffolding is needed to achieve chromosome-level assemblies. We generated PacBio long-read data of the genomes of three relatives of the model plant Arabidopsis thaliana and assembled all three genomes into only a few hundred contigs. To improve the contiguities of these assemblies, we generated BioNano Genomics optical mapping and Dovetail Genomics chromosome conformation capture data for genome scaffolding...
February 3, 2017: Genome Research
https://www.readbyqxmd.com/read/28139673/how-best-to-identify-chromosomal-interactions-a-comparison-of-approaches
#5
James O J Davies, A Marieke Oudelaar, Douglas R Higgs, Jim R Hughes
Chromosome conformation capture (3C) methods are central to understanding the link between nuclear structure and function, and the physical interactions between distal regulatory elements and promoters. However, no one method is appropriate to address all biological questions, as each variant differs markedly in resolution, reproducibility, throughput and biases. A thorough appreciation of the strengths and weaknesses of each technique is critical when choosing the correct method for a specific application or for gauging how best to interpret different sources of data...
January 31, 2017: Nature Methods
https://www.readbyqxmd.com/read/28137286/chrom3d-three-dimensional-genome-modeling-from-hi-c-and-nuclear-lamin-genome-contacts
#6
Jonas Paulsen, Monika Sekelja, Anja R Oldenburg, Alice Barateau, Nolwenn Briand, Erwan Delbarre, Akshay Shah, Anita L Sørensen, Corinne Vigouroux, Brigitte Buendia, Philippe Collas
Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells...
January 30, 2017: Genome Biology
https://www.readbyqxmd.com/read/28135255/massively-multiplex-single-cell-hi-c
#7
Vijay Ramani, Xinxian Deng, Ruolan Qiu, Kevin L Gunderson, Frank J Steemers, Christine M Disteche, William S Noble, Zhijun Duan, Jay Shendure
We present single-cell combinatorial indexed Hi-C (sciHi-C), a method that applies combinatorial cellular indexing to chromosome conformation capture. In this proof of concept, we generate and sequence six sciHi-C libraries comprising a total of 10,696 single cells. We use sciHi-C data to separate cells by karyotypic and cell-cycle state differences and identify cell-to-cell heterogeneity in mammalian chromosomal conformation. Our results demonstrate that combinatorial indexing is a generalizable strategy for single-cell genomics...
January 30, 2017: Nature Methods
https://www.readbyqxmd.com/read/28131315/retrieving-chromatin-patterns-from-deep-sequencing-data-using-correlation-functions
#8
Jana Molitor, Jan-Philipp Mallm, Karsten Rippe, Fabian Erdel
Epigenetic modifications and other chromatin features partition the genome on multiple length scales. They define chromatin domains with distinct biological functions that come in sizes ranging from single modified DNA bases to several megabases in the case of heterochromatic histone modifications. Due to chromatin folding, domains that are well separated along the linear nucleosome chain can form long-range interactions in three-dimensional space. It has now become a routine task to map epigenetic marks and chromatin structure by deep sequencing methods...
February 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28129029/chromosome-conformation-and-gene-expression-patterns-differ-profoundly-in-human-fibroblasts-grown-in-spheroids-versus-monolayers
#9
Haiming Chen, Laura Seaman, Sijia Liu, Thomas Ried, Indika Rajapakse
Human cells derived for in vitro cultures are conventionally grown as adherent monolayers (2 D) which do not resemble natural three dimensional (3 D) tissue architecture. We examined genome structure with chromosome conformation capture (Hi-C) and gene expression with RNA-seq in fibroblasts derived from human foreskin grown in 2 D and 3 D conditions. Our combined analysis of Hi-C and RNA-seq data shows a large number of differentially expressed genes between 2 D and 3 D cells, and these changes are localized in genomic regions that displayed structural changes...
January 27, 2017: Nucleus
https://www.readbyqxmd.com/read/28126037/molecular-dissection-of-germline-chromothripsis-in-a-developmental-context-using-patient-derived-ips-cells
#10
Sjors Middelkamp, Sebastiaan van Heesch, A Koen Braat, Joep de Ligt, Maarten van Iterson, Marieke Simonis, Markus J van Roosmalen, Martijn J E Kelder, Evelien Kruisselbrink, Ron Hochstenbach, Nienke E Verbeek, Elly F Ippel, Youri Adolfs, R Jeroen Pasterkamp, Wigard P Kloosterman, Ewart W Kuijk, Edwin Cuppen
BACKGROUND: Germline chromothripsis causes complex genomic rearrangements that are likely to affect multiple genes and their regulatory contexts. The contribution of individual rearrangements and affected genes to the phenotypes of patients with complex germline genomic rearrangements is generally unknown. METHODS: To dissect the impact of germline chromothripsis in a relevant developmental context, we performed trio-based RNA expression analysis on blood cells, induced pluripotent stem cells (iPSCs), and iPSC-derived neuronal cells from a patient with de novo germline chromothripsis and both healthy parents...
January 26, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28108933/modelling-genome-wide-topological-associating-domains-in-mouse-embryonic-stem-cells
#11
REVIEW
Y Zhan, L Giorgetti, G Tiana
Chromosome conformation capture (3C)-based techniques such as chromosome conformation capture carbon copy (5C) and Hi-C revealed that the folding of mammalian chromosomes is highly hierarchical. A fundamental structural unit in the hierarchy is represented by topologically associating domains (TADs), sub-megabase regions of the genome within which the chromatin fibre preferentially interacts. 3C-based methods provide the mean contact probabilities between chromosomal loci, averaged over a large number of cells, and do not give immediate access to the single-cell conformations of the chromatin fibre...
January 20, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28078515/capturing-genomic-relationships-that-matter
#12
REVIEW
Cameron S Osborne, Borbála Mifsud
There is a strong interrelationship within the cell nucleus between form and function of the genome. This connection is exhibited across multiple hierarchies, ranging from grand-scale positioning of chromosomes and their intersection with specific nuclear functional activities, the segregation of chromosome structure into distinct domains and long-range regulatory contacts that drive spatial and temporal expression patterns of genes. Fifteen years ago, the development of the chromosome conformation capture method placed the nature of specific, long-range regulatory interactions under scrutiny...
January 11, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28057745/reciprocal-insulation-analysis-of-hi-c-data-shows-that-tads-represent-a-functionally-but-not-structurally-privileged-scale-in-the-hierarchical-folding-of-chromosomes
#13
Yinxiu Zhan, Luca Mariani, Iros Barozzi, Edda G Schulz, Nils Bluthgen, Michael Stadler, Guido Tiana, Luca Giorgetti
Understanding how regulatory sequences interact in the context of chromosomal architecture is a central challenge in biology. Chromosome conformation capture revealed that mammalian chromosomes possess a rich hierarchy of structural layers, from multi-megabase compartments to sub-megabase topologically associating domains (TADs) and sub-TAD contact domains. TADs appear to act as regulatory microenvironments by constraining and segregating regulatory interactions across discrete chromosomal regions. However, it is unclear whether other (or all) folding layers share similar properties, or rather TADs constitute a privileged folding scale with maximal impact on the organization of regulatory interactions...
January 5, 2017: Genome Research
https://www.readbyqxmd.com/read/28027298/inferential-structure-determination-of-chromosomes-from-single-cell-hi-c-data
#14
Simeon Carstens, Michael Nilges, Michael Habeck
Chromosome conformation capture (3C) techniques have revealed many fascinating insights into the spatial organization of genomes. 3C methods typically provide information about chromosomal contacts in a large population of cells, which makes it difficult to draw conclusions about the three-dimensional organization of genomes in individual cells. Recently it became possible to study single cells with Hi-C, a genome-wide 3C variant, demonstrating a high cell-to-cell variability of genome organization. In principle, restraint-based modeling should allow us to infer the 3D structure of chromosomes from single-cell contact data, but suffers from the sparsity and low resolution of chromosomal contacts...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27956170/in-trans-promoter-activation-by-enhancers-in-transient-transfection
#15
N A Smirnov, S B Akopov, D A Didych, L G Nikolaev
Earlier, it was reported that the strong cytomegalovirus enhancer can activate the cytomegalovirus promoter in trans, i.e. as a separate plasmid co-transfected with a promoter-reporter gene construct. Here we demonstrate that the ability of enhancers to activate promoters in trans in transient transfection experiments is a property of not only viral regulatory elements but also of various genomic enhancers and promoters. Enhancer-promoter activation in trans is promoter- and cell type-specific, and accompanied by physical interaction between promoter and enhancer as revealed by chromosome conformation capture assays...
March 1, 2017: Gene
https://www.readbyqxmd.com/read/27940490/exploiting-native-forces-to-capture-chromosome-conformation-in-mammalian-cell-nuclei
#16
Lilija Brant, Theodore Georgomanolis, Milos Nikolic, Chris A Brackley, Petros Kolovos, Wilfred van Ijcken, Frank G Grosveld, Davide Marenduzzo, Argyris Papantonis
Mammalian interphase chromosomes fold into a multitude of loops to fit the confines of cell nuclei, and looping is tightly linked to regulated function. Chromosome conformation capture (3C) technology has significantly advanced our understanding of this structure-to-function relationship. However, all 3C-based methods rely on chemical cross-linking to stabilize spatial interactions. This step remains a "black box" as regards the biases it may introduce, and some discrepancies between microscopy and 3C studies have now been reported...
December 9, 2016: Molecular Systems Biology
https://www.readbyqxmd.com/read/27936932/disruption-of-the-3d-cancer-genome-blueprint
#17
Joanna Achinger-Kawecka, Susan J Clark
Recent advances in chromosome conformation capture technologies are improving the current appreciation of how 3D genome architecture affects its function in different cell types and disease. Long-range chromatin interactions are organized into topologically associated domains, which are known to play a role in constraining gene expression patterns. However, in cancer cells there are alterations in the 3D genome structure, which impacts on gene regulation. Disruption of topologically associated domains architecture can result in alterations in chromatin interactions that bring new regulatory elements and genes together, leading to altered expression of oncogenes and tumor suppressor genes...
January 2017: Epigenomics
https://www.readbyqxmd.com/read/27923366/3c-digital-pcr-for-quantification-of-chromatin-interactions
#18
Meijun Du, Liang Wang
BACKGROUND: Chromosome conformation capture (3C) is a powerful and widely used technique for detecting the physical interactions between chromatin regions in vivo. The principle of 3C is to convert physical chromatin interactions into specific DNA ligation products, which are then detected by quantitative polymerase chain reaction (qPCR). However, 3C-qPCR assays are often complicated by the necessity of normalization controls to correct for amplification biases. In addition, qPCR is often limited to a certain cycle number, making it difficult to detect fragment ligations with low frequency...
December 6, 2016: BMC Molecular Biology
https://www.readbyqxmd.com/read/27919068/capturing-pairwise-and-multi-way-chromosomal-conformations-using-chromosomal-walks
#19
Pedro Olivares-Chauvet, Zohar Mukamel, Aviezer Lifshitz, Omer Schwartzman, Noa Oded Elkayam, Yaniv Lubling, Gintaras Deikus, Robert P Sebra, Amos Tanay
Chromosomes are folded into highly compacted structures to accommodate physical constraints within nuclei and to regulate access to genomic information. Recently, global mapping of pairwise contacts showed that loops anchoring topological domains (TADs) are highly conserved between cell types and species. Whether pairwise loops synergize to form higher-order structures is still unclear. Here we develop a conformation capture assay to study higher-order organization using chromosomal walks (C-walks) that link multiple genomic loci together into proximity chains in human and mouse cells...
December 8, 2016: Nature
https://www.readbyqxmd.com/read/27903283/systematic-analysis-of-chromatin-interactions-at-disease-associated-loci-links-novel-candidate-genes-to-inflammatory-bowel-disease
#20
Claartje A Meddens, Magdalena Harakalova, Noortje A M van den Dungen, Hassan Foroughi Asl, Hemme J Hijma, Edwin P J G Cuppen, Johan L M Björkegren, Folkert W Asselbergs, Edward E S Nieuwenhuis, Michal Mokry
BACKGROUND: Genome-wide association studies (GWAS) have revealed many susceptibility loci for complex genetic diseases. For most loci, the causal genes have not been identified. Currently, the identification of candidate genes is predominantly based on genes that localize close to or within identified loci. We have recently shown that 92 of the 163 inflammatory bowel disease (IBD)-loci co-localize with non-coding DNA regulatory elements (DREs). Mutations in DREs can contribute to IBD pathogenesis through dysregulation of gene expression...
November 30, 2016: Genome Biology
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