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topologically associated domains

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https://www.readbyqxmd.com/read/28334818/chromosomal-dynamics-predicted-by-an-elastic-network-model-explains-genome-wide-accessibility-and-long-range-couplings
#1
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...
March 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334773/a-critical-assessment-of-topologically-associating-domain-prediction-tools
#2
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...
March 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28323041/quantitative-analyses-of-the-3d-nuclear-landscape-recorded-with-super-resolved-fluorescence-microscopy
#3
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
#4
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
https://www.readbyqxmd.com/read/28315703/molecular-endocrinology-of-vitamin-d-on-the-epigenome-level
#5
REVIEW
Carsten Carlberg
The molecular endocrinology of vitamin D is based on the facts that i) its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is the high affinity ligand of the nuclear receptor vitamin D receptor (VDR) and ii) the transcription factor VDR is the unique target of 1,25(OH)2D3 in the nucleus. Short-term alterations of the epigenome are primarily changes in the post-translational modification status of nucleosome-forming histone proteins, the consequences of which are i) a local increase or decrease in chromatin accessibility and ii) the activation or repression of gene transcription...
March 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28303076/multi-slicing-strategy-for-the-three-dimensional-discontinuity-layout-optimization-3d-dlo
#6
Yiming Zhang
Discontinuity layout optimization (DLO) is a recently presented topology optimization method for determining the critical layout of discontinuities and the associated upper bound limit load for plane two-dimensional and three-dimensional (3D) problems. The modelling process (pre-processing) for DLO includes defining the discontinuities inside a specified domain and building the target function and the global constraint matrix for the optimization solver, which has great influence on the the efficiency of the computation processes and the reliability of the final results...
March 2017: International Journal for Numerical and Analytical Methods in Geomechanics
https://www.readbyqxmd.com/read/28297879/packing-loops-into-annular-cavities
#7
T A Sobral, M A F Gomes
The continuous packing of a flexible rod in two-dimensional cavities yields a countable set of interacting domains that resembles nonequilibrium cellular systems and belongs to a new class of lightweight material. However, the link between the length of the rod and the number of domains requires investigation, especially in the case of non-simply connected cavities, where the number of avoided regions emulates an effective topological temperature. In the present article we report the results of an experiment of injection of a single flexible rod into annular cavities in order to find the total length needed to insert a given number of loops (domains of one vertex)...
February 2017: Physical Review. E
https://www.readbyqxmd.com/read/28295210/cnvs-analysis-in-a-cohort-of-isolated-and-syndromic-dd-id-reveals-novel-genomic-disorders-position-effects-and-candidate-disease-genes
#8
Eleonora Di Gregorio, Evelise Riberi, Elga Fabia Belligni, Elisa Biamino, Malte Spielmann, Ugo Ala, Alessandro Calcia, Irene Bagnasco, Diana Carli, Giorgia Gai, Mara Giordano, Andrea Guala, Roberto Keller, Giorgia Mandrile, Carlo Arduino, Antonella Maffè, Valeria Giorgia Naretto, Fabio Sirchia, Lorena Sorasio, Silvana Ungari, Andrea Zonta, Giulia Zacchetti, Flavia Talarico, Patrizia Pappi, Simona Cavalieri, Elisa Giorgio, Cecilia Mancini, Marta Ferrero, Alessandro Brussino, Elisa Savin, Marina Gandione, Alessandra Pelle, Daniela Francesca Giachino, Mario De Marchi, Gabriella Restagno, Paolo Provero, Margherita Cirillo Silengo, Enrico Grosso, Joseph D Buxbaum, Barbara Pasini, Silvia De Rubeis, Alfredo Brusco, Giovanni Battista Ferrero
Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect Copy Number Variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes...
March 14, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28289288/3d-structures-of-individual-mammalian-genomes-studied-by-single-cell-hi-c
#9
Tim J Stevens, David Lando, Srinjan Basu, Liam P Atkinson, Yang Cao, Steven F Lee, Martin Leeb, Kai J Wohlfahrt, Wayne Boucher, Aoife O'Shaughnessy-Kirwan, Julie Cramard, Andre J Faure, Meryem Ralser, Enrique Blanco, Lluis Morey, Miriam Sansó, Matthieu G S Palayret, Ben Lehner, Luciano Di Croce, Anton Wutz, Brian Hendrich, Dave Klenerman, Ernest D Laue
The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell...
March 13, 2017: Nature
https://www.readbyqxmd.com/read/28282436/regions-of-very-low-h3k27me3-partition-the-drosophila-genome-into-topological-domains
#10
Sherif El-Sharnouby, Bettina Fischer, Jose Paolo Magbanua, Benjamin Umans, Rosalyn Flower, Siew Woh Choo, Steven Russell, Robert White
It is now well established that eukaryote genomes have a common architectural organization into topologically associated domains (TADs) and evidence is accumulating that this organization plays an important role in gene regulation. However, the mechanisms that partition the genome into TADs and the nature of domain boundaries are still poorly understood. We have investigated boundary regions in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing moderate-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive...
2017: PloS One
https://www.readbyqxmd.com/read/28252665/chromatin-states-shape-insertion-profiles-of-the-piggybac-tol2-and-sleeping-beauty-transposons-and-murine-leukemia-virus
#11
Junko Yoshida, Keiko Akagi, Ryo Misawa, Chikara Kokubu, Junji Takeda, Kyoji Horie
DNA transposons and retroviruses are versatile tools in functional genomics and gene therapy. To facilitate their application, we conducted a genome-wide insertion site profiling of the piggyBac (PB), Tol2 and Sleeping Beauty (SB) transposons and the murine leukemia virus (MLV) in mouse embryonic stem cells (ESCs). PB and MLV preferred highly expressed genes, whereas Tol2 and SB preferred weakly expressed genes. However, correlations with DNase I hypersensitive sites were different for all vectors, indicating that chromatin accessibility is not the sole determinant...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28251877/genomic-landscape-of-cpg-rich-elements-in-human
#12
Vladimir N Babenko, Irina V Chadaeva, Yuriy L Orlov
BACKGROUND: The studies on CpG islands (CGI) and Alu elements functions, evolution, and distribution in the genome started since the discovery in nineteen eighties (1981, 1986, correspondingly). Their highly skewed genome wide distribution implies the non-random retrotransposition pattern. Besides CGIs in gene promoters, CGIs clusters were observed in the homeobox gene regions and in the macrosatellites, but the whole picture of their distribution specifics was not grasped. Attempts to identify any causative features upon their (genome wide) distribution, such as the DNA context mediated preferred insertion sites of Alu repeats, have been made to ascribe their clusters location...
February 7, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28251841/topologically-associated-domains-a-successful-scaffold-for-the-evolution-of-gene-regulation-in-animals
#13
REVIEW
Rafael D Acemel, Ignacio Maeso, José Luis Gómez-Skarmeta
The evolution of gene regulation is considered one of the main drivers causing the astonishing morphological diversity in the animal kingdom. Gene regulation in animals heavily depends upon cis-regulatory elements, discrete pieces of DNA that interact with target promoters to regulate gene expression. In the last years, Chromosome Conformation Capture experiments (4C-seq, 5C, and HiC) in several organisms have shown that the genomes of many bilaterian animals are organized in the 3D chromatin space in compartments called topologically associated domains (TADs)...
March 2, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28249171/cis-acting-complex-trait-associated-lincrna-expression-correlates-with-modulation-of-chromosomal-architecture
#14
Jennifer Yihong Tan, Adam Alexander Thil Smith, Maria Ferreira da Silva, Cyril Matthey-Doret, Rico Rueedi, Reyhan Sönmez, David Ding, Zoltán Kutalik, Sven Bergmann, Ana Claudia Marques
Intergenic long noncoding RNAs (lincRNAs) are the largest class of transcripts in the human genome. Although many have recently been linked to complex human traits, the underlying mechanisms for most of these transcripts remain undetermined. We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant lincRNAs (TR-lincRNAs) in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28222386/heterogeneous-fractionation-profiles-of-meta-analytic-coactivation-networks
#15
Angela R Laird, Michael C Riedel, Mershack Okoe, Radu Jianu, Kimberly L Ray, Simon B Eickhoff, Stephen M Smith, Peter T Fox, Matthew T Sutherland
Computational cognitive neuroimaging approaches can be leveraged to characterize the hierarchical organization of distributed, functionally specialized networks in the human brain. To this end, we performed large-scale mining across the BrainMap database of coordinate-based activation locations from over 10,000 task-based experiments. Meta-analytic coactivation networks were identified by jointly applying independent component analysis (ICA) and meta-analytic connectivity modeling (MACM) across a wide range of model orders (i...
February 18, 2017: NeuroImage
https://www.readbyqxmd.com/read/28221284/pain-interference-and-physical-function-demonstrate-poor-longitudinal-association-in-people-living-with-pain-a-promis-investigation
#16
Nicholas V Karayannis, John A Sturgeon, Ming Chih-Kao, Corinne Cooley, Sean C Mackey
A primary goal in managing pain is to reduce pain and increase physical function (PF). This goal is also tied to continuing payment for treatment services in many practice guidelines. Pain interference (PI) is often used as a proxy for measurement and reporting of PF in these guidelines. A common assumption is that reductions in PI will translate into improvement in PF over time. This assumption needs to be tested in a clinical environment. Consequently, we used the patient reported outcomes measurement information system (PROMIS) to describe the topology of the longitudinal relationship between PI in relation to PF...
February 16, 2017: Pain
https://www.readbyqxmd.com/read/28167501/comprehensive-characterization-of-neutrophil-genome-topology
#17
Yina Zhu, Ke Gong, Matthew Denholtz, Vivek Chandra, Mark P Kamps, Frank Alber, Cornelis Murre
Neutrophils are responsible for the first line of defense against invading pathogens. Their nuclei are uniquely structured as multiple lobes that establish a highly constrained nuclear environment. Here we found that neutrophil differentiation was not associated with large-scale changes in the number and sizes of topologically associating domains (TADs). However, neutrophil genomes were enriched for long-range genomic interactions that spanned multiple TADs. Population-based simulation of spherical and toroid genomes revealed declining radii of gyration for neutrophil chromosomes...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28167211/an-insight-into-the-orphan-nucleotide-sugar-transporter-slc35a4
#18
Paulina Sosicka, Dorota Maszczak-Seneczko, Bożena Bazan, Yauhen Shauchuk, Beata Kaczmarek, Mariusz Olczak
SLC35A4 has been classified in the SLC35A subfamily based on amino acid sequence homology. Most of the proteins belonging to the SLC35 family act as transporters of nucleotide sugars. In this study, the subcellular localization of endogenous SLC35A4 was determined via immunofluorescence staining, and it was demonstrated that SLC35A4 localizes mainly to the Golgi apparatus. In silico topology prediction suggests that SLC35A4 has an uneven number of transmembrane domains and its N-terminus is directed towards the Golgi lumen...
May 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28157505/polycomb-repressive-complex-1-generates-discrete-compacted-domains-that-change-during-differentiation
#19
Sharmistha Kundu, Fei Ji, Hongjae Sunwoo, Gaurav Jain, Jeannie T Lee, Ruslan I Sadreyev, Job Dekker, Robert E Kingston
Master regulatory genes require stable silencing by the polycomb group (PcG) to prevent misexpression during differentiation and development. Some PcG proteins covalently modify histones, which contributes to heritable repression. The role for other effects on chromatin structure is less understood. We characterized the organization of PcG target genes in ESCs and neural progenitors using 5C and super-resolution microscopy. The genomic loci of repressed PcG targets formed discrete, small (20-140 Kb) domains of tight interaction that corresponded to locations bound by canonical polycomb repressive complex 1 (PRC1)...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28154080/bacillus-subtilis-smc-complexes-juxtapose-chromosome-arms-as-they-travel-from-origin-to-terminus
#20
Xindan Wang, Hugo B Brandão, Tung B K Le, Michael T Laub, David Z Rudner
Structural maintenance of chromosomes (SMC) complexes play critical roles in chromosome dynamics in virtually all organisms, but how they function remains poorly understood. In the bacterium Bacillus subtilis, SMC-condensin complexes are topologically loaded at centromeric sites adjacent to the replication origin. Here we provide evidence that these ring-shaped assemblies tether the left and right chromosome arms together while traveling from the origin to the terminus (>2 megabases) at rates >50 kilobases per minute...
February 3, 2017: Science
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