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topologically associated domains

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https://www.readbyqxmd.com/read/28941661/molecular-analysis-of-human-solute-carrier-slc26-anion-transporter-disease-causing-mutations-using-3-dimensional-homology-modeling
#1
Chloe Rapp, Xiaoyun Bai, Reinhart A F Reithmeier
The availability of the first crystal structure of a bacterial member (SLC26Dg) of the solute carrier SLC26 family of anion transporters has allowed us to create 3-dimensional models of all 10 human members (SLC26A1-A11, A10 being a pseudogene) of these membrane proteins using the Phyre2 bioinformatic tool. The homology modeling predicted that the SLC26 human proteins, like the SLC26Dg template, all consist of 14 transmembrane segments (TM) arranged in a 7+7 inverted topology with the amino-termini of two half-helices (TM3 and 10) facing each other in the centre of the protein to create the anion-binding site, linked to a C-terminal cytosolic sulfate transporter anti-sigma factor antagonist (STAS) domain...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28939693/mass-spectrometry-techniques-for-studying-the-ubiquitin-system
#2
REVIEW
Rachel E Heap, Megan S Gant, Frederic Lamoliatte, Julien Peltier, Matthias Trost
Post-translational control of proteins through covalent attachment of ubiquitin plays important roles in all eukaryotic cell functions. The ubiquitin system in humans consists of 2 E1, 35 E2 and >600 E3 ubiquitin ligases as well as hundreds of deubiquitylases, which reverse ubiquitin attachment. Moreover, there are hundreds of proteins with ubiquitin-binding domains that bind one of the eight possible polyubiquitin chains. Dysfunction of the ubiquitin system is associated with many diseases such as cancer, autoimmunity and neurodegeneration, demonstrating the importance of ubiquitylation...
September 22, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28938092/ctcf-mediated-enhancer-promoter-interaction-is-a-critical-regulator-of-cell-to-cell-variation-of-gene-expression
#3
Gang Ren, Wenfei Jin, Kairong Cui, Joseph Rodrigez, Gangqing Hu, Zhiying Zhang, Daniel R Larson, Keji Zhao
Recent studies indicate that even a homogeneous population of cells display heterogeneity in gene expression and response to environmental stimuli. Although promoter structure critically influences the cell-to-cell variation of gene expression in bacteria and lower eukaryotes, it remains unclear what controls the gene expression noise in mammals. Here we report that CTCF decreases cell-to-cell variation of expression by stabilizing enhancer-promoter interaction. We show that CTCF binding sites are interwoven with enhancers within topologically associated domains (TADs) and a positive correlation is found between CTCF binding and the activity of the associated enhancers...
September 21, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28936982/optimization-and-quality-control-of-genome-wide-hi-c-library-preparation
#4
Xiang-Yuan Zhang, Chao He, Bing-Yu Ye, De-Jian Xie, Ming-Lei Shi, Yan Zhang, Wen-Long Shen, Ping Li, Zhi-Hu Zhao
Highest-throughput chromosome conformation capture (Hi-C) is one of the key assays for genome- wide chromatin interaction studies. It is a time-consuming process that involves many steps and many different kinds of reagents, consumables, and equipments. At present, the reproducibility is unsatisfactory. By optimizing the key steps of the Hi-C experiment, such as crosslinking, pretreatment of digestion, inactivation of restriction enzyme, and in situ ligation etc., we established a robust Hi-C procedure and prepared two biological replicates of Hi-C libraries from the GM12878 cells...
September 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28927344/structural-elucidation-of-transmembrane-domain-zero-tmd0-of-ecdl-a-multidrug-resistance-associated-protein-mrp-family-of-atp-binding-cassette-transporter-protein-revealed-by-atomistic-simulation
#5
Krishnendu Bera, Priyanka Rani, Gaurav Kishor, Shikha Agarwal, Antresh Kumar, Durg Vijay Singh
ATP-Binding cassette (ABC) transporters play an extensive role in the translocation of diverse sets of biologically important molecules across membrane. EchnocandinB (antifungal) and EcdL protein of Aspergillus rugulosus are encoded by the same cluster of genes. Co-expression of EcdL and echinocandinB reflects tightly linked biological functions. EcdL belongs to Multidrug Resistance associated Protein (MRP) subfamily of ABC transporters with an extra transmembrane domain zero (TMD0). Complete structure of MRP subfamily comprising of TMD0 domain, at atomic resolution is not known...
September 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28925965/studying-the-structural-significance-of-galectin-design-by-playing-a-modular-puzzle-homodimer-generation-from-human-tandem-repeat-type-heterodimeric-galectin-8-by-domain-shuffling
#6
Anna-Kristin Ludwig, Malwina Michalak, Nadya Shilova, Sabine André, Herbert Kaltner, Nicolai V Bovin, Jürgen Kopitz, Hans-Joachim Gabius
Tissue lectins are emerging (patho)physiological effectors with broad significance. The capacity of adhesion/growth-regulatory galectins to form functional complexes with distinct cellular glycoconjugates is based on molecular selection of matching partners. Engineering of variants by changing the topological display of carbohydrate recognition domains (CRDs) provides tools to understand the inherent specificity of the functional pairing. We here illustrate its practical implementation in the case of human tandem-repeat-type galectin-8 (Gal-8)...
September 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28918933/structural-proteomics-topology-and-relative-accessibility-of-plant-lipid-droplet-associated-proteins
#7
Pascale Jolivet, Laure Aymé, Alexandre Giuliani, Frank Wien, Thierry Chardot, Yann Gohon
Lipid droplets are the major stock of lipids in oleaginous plant seeds. Despite their economic importance for oil production and biotechnological issues (biofuels, lubricants and plasticizers), numerous questions about their formation, structure and regulation are still unresolved. To determine water accessible domains of protein coating at lipid droplets surface, a structural proteomic approach has been performed. This technique relies on the millisecond timescale production of hydroxyl radicals by the radiolysis of water using Synchrotron X-ray white beam...
September 14, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28912419/identifying-topologically-associating-domains-and-subdomains-by-gaussian-mixture-model-and-proportion-test
#8
Wenbao Yu, Bing He, Kai Tan
The spatial organization of the genome plays a critical role in regulating gene expression. Recent chromatin interaction mapping studies have revealed that topologically associating domains and subdomains are fundamental building blocks of the three-dimensional genome. Identifying such hierarchical structures is a critical step toward understanding the three-dimensional structure-function relationship of the genome. Existing computational algorithms lack statistical assessment of domain predictions and are computationally inefficient for high-resolution Hi-C data...
September 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28910577/subnuclear-distribution-of-proteins-links-with-genome-architecture
#9
Fouziya R Shah, Younus A Bhat, Ajazul H Wani
Metazoan genomes have a hierarchal 3-dimensional (3D) organization scaling from nucleosomes, loops, topologically associating domains (TADs), compartments, to chromosome territories. The 3D organization of genome has been linked with development, differentiation and disease. However, the principles governing the 3D chromatin architecture are just beginning to get unraveled. The nucleus has very high concentration of proteins and these proteins are either diffusely distributed throughout the nucleus, or aggregated in the form of foci/bodies/clusters/speckles or in combination of both...
September 14, 2017: Nucleus
https://www.readbyqxmd.com/read/28904177/limited-proteolysis-as-a-tool-to-probe-the-tertiary-conformation-of-dysferlin-and-structural-consequences-of-patient-missense-variant-l344p
#10
Natalie Woolger, Adam Bournazos, Reece A Sophocleous, Frances J Evesson, Angela Lek, Birgit Driemer, R Bryan Sutton, Sandra T Cooper
Dysferlin is a large transmembrane protein that plays a key role in cell membrane repair, and underlies a recessive form of inherited muscular dystrophy. Dysferlinopathy is characterized by absence or marked reduction of dysferlin protein, with 43% of reported pathogenic variants being missense variants that span the length of the dysferlin protein. The unique structure of dysferlin, with seven tandem C2-domains separated by linkers, suggest dysferlin may dynamically associate with phospholipid membranes in response to Ca2+ signaling...
September 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28902867/analysis-of-the-relationship-between-coexpression-domains-and-chromatin-3d-organization
#11
María E Soler-Oliva, Jose A Guerrero-Martínez, Valentina Bachetti, Jose C Reyes
Gene order is not random in eukaryotic chromosomes, and co-regulated genes tend to be clustered. The mechanisms that determine co-regulation of large regions of the genome and its connection with chromatin three-dimensional (3D) organization are still unclear however. Here we have adapted a recently described method for identifying chromatin topologically associating domains (TADs) to identify coexpression domains (which we term "CODs"). Using human normal breast and breast cancer RNA-seq data, we have identified approximately 500 CODs...
September 13, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28882594/terbinafine-is-a-novel-and-selective-activator-of-the-two-pore-domain-potassium-channel-task3
#12
Paul D Wright, Emma L Veale, David McCoull, David C Tickle, Jonathan M Large, Emma Ococks, Gemma Gothard, Catherine Kettleborough, Alistair Mathie, Jeffrey Jerman
Two-pore domain potassium channels (K2Ps) are characterized by their four transmembrane domain and two-pore topology. They carry background (or leak) potassium current in a variety of cell types. Despite a number of important roles there is currently a lack of pharmacological tools with which to further probe K2P function. We have developed a cell-based thallium flux assay, using baculovirus delivered TASK3 (TWIK-related acid-sensitive K(+) channel 3, KCNK9, K2P9.1) with the aim of identifying novel, selective TASK3 activators...
September 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28874668/topologically-associating-domains-are-ancient-features-that-coincide-with-metazoan-clusters-of-extreme-noncoding-conservation
#13
Nathan Harmston, Elizabeth Ing-Simmons, Ge Tan, Malcolm Perry, Matthias Merkenschlager, Boris Lenhard
Developmental genes in metazoan genomes are surrounded by dense clusters of conserved noncoding elements (CNEs). CNEs exhibit unexplained extreme levels of sequence conservation, with many acting as developmental long-range enhancers. Clusters of CNEs define the span of regulatory inputs for many important developmental regulators and have been described previously as genomic regulatory blocks (GRBs). Their function and distribution around important regulatory genes raises the question of how they relate to 3D conformation of these loci...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28867287/dynamic-control-of-x-chromosome-conformation-and-repression-by-a-histone-h4k20-demethylase
#14
Katjuša Brejc, Qian Bian, Satoru Uzawa, Bayly S Wheeler, Erika C Anderson, David S King, Philip J Kranzusch, Christine G Preston, Barbara J Meyer
Chromatin modification and higher-order chromosome structure play key roles in gene regulation, but their functional interplay in controlling gene expression is elusive. We have discovered the machinery and mechanism underlying the dynamic enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during C. elegans dosage compensation and demonstrated H4K20me1's pivotal role in regulating higher-order chromosome structure and X-chromosome-wide gene expression. The structure and the activity of the dosage compensation complex (DCC) subunit DPY-21 define a Jumonji demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28863138/5c-analysis-of-the-epidermal-differentiation-complex-locus-reveals-distinct-chromatin-interaction-networks-between-gene-rich-and-gene-poor-tads-in-skin-epithelial-cells
#15
Krzysztof Poterlowicz, Joanne L Yarker, Igor Malashchuk, Brian R Lajoie, Andrei N Mardaryev, Michal R Gdula, Andrey A Sharov, Terumi Kohwi-Shigematsu, Vladimir A Botchkarev, Michael Y Fessing
Mammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28826674/evolutionarily-conserved-principles-predict-3d-chromatin-organization
#16
M Jordan Rowley, Michael H Nichols, Xiaowen Lyu, Masami Ando-Kuri, I Sarahi M Rivera, Karen Hermetz, Ping Wang, Yijun Ruan, Victor G Corces
Topologically associating domains (TADs), CTCF loop domains, and A/B compartments have been identified as important structural and functional components of 3D chromatin organization, yet the relationship between these features is not well understood. Using high-resolution Hi-C and HiChIP, we show that Drosophila chromatin is organized into domains we term compartmental domains that correspond precisely with A/B compartments at high resolution. We find that transcriptional state is a major predictor of Hi-C contact maps in several eukaryotes tested, including C...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28802249/high-resolution-mapping-of-chromatin-conformation-in-cardiac-myocytes-reveals-structural-remodeling-of-the-epigenome-in-heart-failure
#17
Manuel Rosa-Garrido, Douglas J Chapski, Anthony D Schmitt, Todd H Kimball, Elaheh Karbassi, Emma Monte, Enrique Balderas, Matteo Pellegrini, Tsai-Ting Shih, Elizabeth Soehalim, David A Liem, Peipei Ping, Niels J Galjart, Shuxun Ren, Yibin Wang, Bing Ren, Thomas M Vondriska
Background -Cardiovascular disease is associated with epigenomic changes in the heart, however the endogenous structure of cardiac myocyte chromatin has never been determined. Methods -To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype...
August 11, 2017: Circulation
https://www.readbyqxmd.com/read/28796201/enhanced-sensitivity-at-higher-order-exceptional-points
#18
Hossein Hodaei, Absar U Hassan, Steffen Wittek, Hipolito Garcia-Gracia, Ramy El-Ganainy, Demetrios N Christodoulides, Mercedeh Khajavikhan
Non-Hermitian degeneracies, also known as exceptional points, have recently emerged as a new way to engineer the response of open physical systems, that is, those that interact with the environment. They correspond to points in parameter space at which the eigenvalues of the underlying system and the corresponding eigenvectors simultaneously coalesce. In optics, the abrupt nature of the phase transitions that are encountered around exceptional points has been shown to lead to many intriguing phenomena, such as loss-induced transparency, unidirectional invisibility, band merging, topological chirality and laser mode selectivity...
August 9, 2017: Nature
https://www.readbyqxmd.com/read/28792605/single-cell-hi-c-bridges-microscopy-and-genome-wide-sequencing-approaches-to-study-3d-chromatin-organization
#19
REVIEW
Sergey V Ulianov, Kikue Tachibana-Konwalski, Sergey V Razin
Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture (3C)-based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, some of which could be transiently stabilized and serve regulatory purposes...
August 9, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28792001/implicating-candidate-genes-at-gwas-signals-by-leveraging-topologically-associating-domains
#20
Gregory P Way, Daniel W Youngstrom, Kurt D Hankenson, Casey S Greene, Struan Fa Grant
Genome-wide association studies (GWAS) have contributed significantly to the understanding of complex disease genetics. However, GWAS only report association signals and do not necessarily identify culprit genes. As most signals occur in non-coding regions of the genome, it is often challenging to assign genomic variants to the underlying causal mechanism(s). Topologically associating domains (TADs) are primarily cell-type-independent genomic regions that define interactome boundaries and can aid in the designation of limits within which an association most likely impacts gene function...
August 9, 2017: European Journal of Human Genetics: EJHG
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