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topologically associated domains

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https://www.readbyqxmd.com/read/28646141/human-sialidase-neu3-is-s-acylated-and-behaves-like-an-integral-membrane-protein
#1
Macarena Rodriguez-Walker, Jose L Daniotti
Membrane-bound sialidase Neu3 is involved in the catabolism of glycoconjugates, and plays crucial roles in numerous biological processes. Since the mechanism of its association with membranes is still not completely understood, the aim of this work was to provide further information regarding this aspect. Human Neu3 was found to be associated with the plasma membrane and endomembranes, and it was not released from the lipid bilayer under conditions that typically release peripheral membrane proteins. By different experimental approaches, we demonstrated that its C-terminus is exposed to the cytosol while another portion of the protein is exposed to the extracellular space, suggesting that Neu3 possesses the features of a transmembrane protein...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630348/analysis-of-a-dual-domain-phosphoglycosyl-transferase-reveals-a-ping-pong-mechanism-with-a-covalent-enzyme-intermediate
#2
Debasis Das, Petr Kuzmic, Barbara Imperiali
Phosphoglycosyl transferases (PGTs) are integral membrane proteins with diverse architectures that catalyze the formation of polyprenol diphosphate-linked glycans via phosphosugar transfer from a nucleotide diphosphate-sugar to a polyprenol phosphate. There are two PGT superfamilies that differ significantly in overall structure and topology. The polytopic PGT superfamily, represented by MraY and WecA, has been the subject of many studies because of its roles in peptidoglycan and O-antigen biosynthesis. In contrast, less is known about a second, extensive superfamily of PGTs that reveals a core structure with dual domain architecture featuring a C-terminal soluble globular domain and a predicted N-terminal membrane-associated domain...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28622508/saf-a-regulates-interphase-chromosome-structure-through-oligomerization-with-chromatin-associated-rnas
#3
Ryu-Suke Nozawa, Lora Boteva, Dinesh C Soares, Catherine Naughton, Alison R Dun, Adam Buckle, Bernard Ramsahoye, Peter C Bruton, Rebecca S Saleeb, Maria Arnedo, Bill Hill, Rory R Duncan, Sutherland K Maciver, Nick Gilbert
Higher eukaryotic chromosomes are organized into topologically constrained functional domains; however, the molecular mechanisms required to sustain these complex interphase chromatin structures are unknown. A stable matrix underpinning nuclear organization was hypothesized, but the idea was abandoned as more dynamic models of chromatin behavior became prevalent. Here, we report that scaffold attachment factor A (SAF-A), originally identified as a structural nuclear protein, interacts with chromatin-associated RNAs (caRNAs) via its RGG domain to regulate human interphase chromatin structures in a transcription-dependent manner...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28615069/regulatory-landscape-fusion-in-rhabdomyosarcoma-through-interactions-between-the-pax3-promoter-and-foxo1-regulatory-elements
#4
Cristina Vicente-García, Barbara Villarejo-Balcells, Ibai Irastorza-Azcárate, Silvia Naranjo, Rafael D Acemel, Juan J Tena, Peter W J Rigby, Damien P Devos, Jose L Gómez-Skarmeta, Jaime J Carvajal
BACKGROUND: The organisation of vertebrate genomes into topologically associating domains (TADs) is believed to facilitate the regulation of the genes located within them. A remaining question is whether TAD organisation is achieved through the interactions of the regulatory elements within them or if these interactions are favoured by the pre-existence of TADs. If the latter is true, the fusion of two independent TADs should result in the rewiring of the transcriptional landscape and the generation of ectopic contacts...
June 14, 2017: Genome Biology
https://www.readbyqxmd.com/read/28604721/comparison-of-computational-methods-for-hi-c-data-analysis
#5
Mattia Forcato, Chiara Nicoletti, Koustav Pal, Carmen Maria Livi, Francesco Ferrari, Silvio Bicciato
Hi-C is a genome-wide sequencing technique used to investigate 3D chromatin conformation inside the nucleus. Computational methods are required to analyze Hi-C data and identify chromatin interactions and topologically associating domains (TADs) from genome-wide contact probability maps. We quantitatively compared the performance of 13 algorithms in their analyses of Hi-C data from six landmark studies and simulations. This comparison revealed differences in the performance of methods for chromatin interaction identification, but more comparable results for TAD detection between algorithms...
June 12, 2017: Nature Methods
https://www.readbyqxmd.com/read/28588707/identification-of-potential-target-genes-associated-with-the-effect-of-propranolol-on-angiosarcoma-via-microarray-analysis
#6
Shiyong Zhou, Pengfei Liu, Wenhua Jiang, Huilai Zhang
The purpose of the present study was to explore the effect of propranolol on angiosarcoma, and the potential target genes involved in the processes of proliferation and differentiation of angiosarcoma tumor cells. The mRNA expression profile (GSE42534) was downloaded from the Gene Expressed Omnibus database, including three samples without propranolol treatment (control), three samples with propranolol treatment for 4 h and three samples with propranolol treatment for 24 h. The differentially expressed genes (DEGs) in angiosarcoma tumor cells with or without propranolol treatment were obtained via the limma package of R and designated DEGs-4 h and DEGs-24 h...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28587632/meta-analysis-of-cell-specific-transcriptomic-data-using-fuzzy-c-means-clustering-discovers-versatile-viral-responsive-genes
#7
Atif Khan, Dejan Katanic, Juilee Thakar
BACKGROUND: Despite advances in the gene-set enrichment analysis methods; inadequate definitions of gene-sets cause a major limitation in the discovery of novel biological processes from the transcriptomic datasets. Typically, gene-sets are obtained from publicly available pathway databases, which contain generalized definitions frequently derived by manual curation. Recently unsupervised clustering algorithms have been proposed to identify gene-sets from transcriptomics datasets deposited in public domain...
June 6, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28581772/dynamical-defects-in-rotating-magnetic-skyrmion-lattices
#8
S Pöllath, J Wild, L Heinen, T N G Meier, M Kronseder, L Tutsch, A Bauer, H Berger, C Pfleiderer, J Zweck, A Rosch, C H Back
The chiral magnet Cu_{2}OSeO_{3} hosts a Skyrmion lattice that may be equivalently described as a superposition of plane waves or a lattice of particlelike topological objects. A thermal gradient may break up the Skyrmion lattice and induce rotating domains, raising the question of which of these scenarios better describes the violent dynamics at the domain boundaries. Here, we show that in an inhomogeneous temperature gradient caused by illumination in a Lorentz transmission electron microscope different parts of the Skyrmion lattice can be set into motion with different angular velocities...
May 19, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28580975/morphological-imperfections-of-epitaxial-graphene-from-a-hindrance-to-the-generation-of-new-photo-responses-in-the-visible-domain
#9
A Ben Gouider Trabelsi, F V Kusmartsev, M B Gaifullin, D M Forrester, A Kusmartseva, M Oueslati
We report the discovery of remarkable photo-physical phenomena with characteristics unique to epitaxial graphene grown on 6H-SiC (000-1). Surprisingly, the electrical resistance of graphene increases under light illumination in contrast to conventional materials where it normally decreases. The resistance shows logarithmic temperature dependences which may be attributed to an Altshuler-Aronov effect. We show that the photoresistance depends on the frequency of the irradiating light, with three lasers (red, green, and violet) used to demonstrate the phenomenon...
June 5, 2017: Nanoscale
https://www.readbyqxmd.com/read/28562241/cooperation-between-a-hierarchical-set-of-recruitment-sites-targets-the-x-chromosome-for-dosage-compensation
#10
Sarah Elizabeth Albritton, Anna-Lena Kranz, Lara Heermans Winterkorn, Lena Annika Street, Sevinc Ercan
In many organisms, it remains unclear how X chromosomes are specified for dosage compensation, since DNA sequence motifs shown to be important for dosage compensation complex (DCC) recruitment are themselves not X-specific. Here, we addressed this problem in C. elegans. We found that the DCC recruiter, SDC-2, is required to maintain open chromatin at a small number of primary DCC recruitment sites, whose sequence and genomic context are X-specific. Along the X, primary recruitment sites are interspersed with secondary sites, whose function is X-dependent...
May 30, 2017: ELife
https://www.readbyqxmd.com/read/28549169/regulatory-dynamics-of-11p13-suggest-a-role-for-ehf-in-modifying-cf-lung-disease-severity
#11
Lindsay R Stolzenburg, Rui Yang, Jenny L Kerschner, Sara Fossum, Matthew Xu, Andrew Hoffmann, Kay-Marie Lamar, Sujana Ghosh, Sarah Wachtel, Shih-Hsing Leir, Ann Harris
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), but are not good predictors of lung phenotype. Genome-wide association studies (GWAS) previously identified additional genomic sites associated with CF lung disease severity. One of these, at chromosome 11p13, is an intergenic region between Ets homologous factor (EHF) and Apaf-1 interacting protein (APIP). Our goal was to determine the functional significance of this region, which being intergenic is probably regulatory...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28534707/type-ia-topoisomerases-can-be-magicians-for-both-dna-and-rna-in-all-domains-of-life
#12
Muzammil Ahmad, Dongyi Xu, Weidong Wang
Topoisomerases solve critical topological problems in DNA metabolism and have long been regarded as the "magicians" of the DNA world. Here we present views from two of our recent studies indicating that Type IA topoisomerases from all domains of life often possess dual topoisomerase activities for both DNA and RNA. In animals, one of the two Type IA topoisomerases, Top3β, contains an RNA-binding domain, possesses RNA topoisomerase activity, binds mRNAs, interacts with mRNA-binding proteins, and associates with active mRNA translation machinery...
May 23, 2017: RNA Biology
https://www.readbyqxmd.com/read/28529872/functional-network-changes-and-cognitive-control-in-schizophrenia
#13
Kimberly L Ray, Tyler A Lesh, Amber M Howell, Taylor P Salo, J Daniel Ragland, Angus W MacDonald, James M Gold, Steven M Silverstein, Deana M Barch, Cameron S Carter
Cognitive control is a cognitive and neural mechanism that contributes to managing the complex demands of day-to-day life. Studies have suggested that functional impairments in cognitive control associated brain circuitry contribute to a broad range of higher cognitive deficits in schizophrenia. To examine this issue, we assessed functional connectivity networks in healthy adults and individuals with schizophrenia performing tasks from two distinct cognitive domains that varied in demands for cognitive control, the RiSE episodic memory task and DPX goal maintenance task...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28525758/targeted-degradation-of-ctcf-decouples-local-insulation-of-chromosome-domains-from-genomic-compartmentalization
#14
Elphège P Nora, Anton Goloborodko, Anne-Laure Valton, Johan H Gibcus, Alec Uebersohn, Nezar Abdennur, Job Dekker, Leonid A Mirny, Benoit G Bruneau
The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28513628/an-integrated-model-for-detecting-significant-chromatin-interactions-from-high-resolution-hi-c-data
#15
Mark Carty, Lee Zamparo, Merve Sahin, Alvaro González, Raphael Pelossof, Olivier Elemento, Christina S Leslie
Here we present HiC-DC, a principled method to estimate the statistical significance (P values) of chromatin interactions from Hi-C experiments. HiC-DC uses hurdle negative binomial regression account for systematic sources of variation in Hi-C read counts-for example, distance-dependent random polymer ligation and GC content and mappability bias-and model zero inflation and overdispersion. Applied to high-resolution Hi-C data in a lymphoblastoid cell line, HiC-DC detects significant interactions at the sub-topologically associating domain level, identifying potential structural and regulatory interactions supported by CTCF binding sites, DNase accessibility, and/or active histone marks...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28510211/insights-into-genome-architecture-deduced-from-the-properties-of-short-lac-repressor-mediated-dna-loops
#16
REVIEW
Pamela J Perez, Wilma K Olson
Genomic DNA is vastly longer than the space allotted to it in a cell. The molecule must fold with a level of organization that satisfies the imposed spatial constraints as well as allow for the processing of genetic information. Key players in this organization include the negative supercoiling of DNA, which facilitates the unwinding of the double-helical molecule, and the associations of DNA with proteins, which partition the DNA into isolated loops, or domains. In order to gain insight into the principles of genome organization and to visualize the folding of spatially constrained DNA, we have developed new computational methods to identify the preferred three-dimensional pathways of protein-mediated DNA loops and to characterize the topological properties of these structures...
November 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28504305/intranuclear-and-higher-order-chromatin-organization-of-the-major-histone-gene-cluster-in-breast-cancer
#17
Andrew J Fritz, Prachi N Ghule, Joseph R Boyd, Coralee E Tye, Natalie A Page, Deli Hong, David J Shirley, Adam S Weinheimer, Ahmet R Barutcu, Diana L Gerrard, Seth Frietze, Andre J van Wijnen, Sayyed K Zaidi, Anthony N Imbalzano, Jane B Lian, Janet L Stein, Gary S Stein
Alterations in nuclear morphology are common in cancer progression. However, the degree to which gross morphological abnormalities translate into compromised higher-order chromatin organization is poorly understood. To explore the functional links between gene expression and chromatin structure in breast cancer, we performed RNA-seq gene expression analysis on the basal breast cancer progression model based on human MCF10A cells. Positional gene enrichment identified the major histone gene cluster at chromosome 6p22 as one of the most significantly upregulated (and not amplified) clusters of genes from the normal-like MCF10A to premalignant MCF10AT1 and metastatic MCF10CA1a cells...
May 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28494440/nuclear-architecture-of-mouse-spermatocytes-chromosome-topology-heterochromatin-and-nucleolus
#18
Soledad Berrios
The nuclear organization of spermatocytes in meiotic prophase I is primarily determined by the synaptic organization of the bivalents that are bound by their telomeres to the nuclear envelope and described as arc-shaped trajectories through the 3D nuclear space. However, over this basic meiotic organization, a spermatocyte nuclear architecture arises that is based on higher-ordered patterns of spatial associations among chromosomal domains from different bivalents that are conditioned by the individual characteristics of chromosomes and the opportunity for interactions between their domains...
2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28487148/direct-observation-of-cell-cycle-dependent-interactions-between-ctcf-and-chromatin
#19
Harsha Agarwal, Matthias Reisser, Celina Wortmann, J Christof M Gebhardt
The three-dimensional arrangement of chromatin encodes regulatory traits important for nuclear processes such as transcription and replication. Chromatin topology is in part mediated by the architectural protein CCCTC-binding factor (CTCF) that binds to the boundaries of topologically associating domains. Whereas sites of CTCF interactions are well characterized, little is known on how long CTCF binds to chromatin and how binding evolves during the cell cycle. We monitored CTCF-chromatin interactions by live cell single molecule tracking in different phases of the cell cycle...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28475897/the-cohesin-release-factor-wapl-restricts-chromatin-loop-extension
#20
Judith H I Haarhuis, Robin H van der Weide, Vincent A Blomen, J Omar Yáñez-Cuna, Mario Amendola, Marjon S van Ruiten, Peter H L Krijger, Hans Teunissen, René H Medema, Bas van Steensel, Thijn R Brummelkamp, Elzo de Wit, Benjamin D Rowland
The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin's DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs)...
May 4, 2017: Cell
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