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topologically associated domains

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https://www.readbyqxmd.com/read/29772275/5c-id-increased-resolution-chromosome-conformation-capture-carbon-copy-with-in-situ-3c-and-double-alternating-primer-design
#1
Ji Hun Kim, Katelyn R Titus, Wanfeng Gong, Jonathan A Beagan, Zhendong Cao, Jennifer E Phillips-Cremins
Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs, and looping interactions. Currently, there is a great need to evaluate the link between chromatin topology and genome function across many biological conditions and genetic perturbations. Hi-C can generate genome-wide maps of looping interactions but is intractable for high-throughput comparison of loops across multiple conditions due to the enormous number of reads (>6 Billion) required per library...
May 14, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29763432/distinctive-types-of-postzygotic-single-nucleotide-mosaicisms-in-healthy-individuals-revealed-by-genome-wide-profiling-of-multiple-organs
#2
August Yue Huang, Xiaoxu Yang, Sheng Wang, Xianing Zheng, Qixi Wu, Adam Yongxin Ye, Liping Wei
Postzygotic single-nucleotide mosaicisms (pSNMs) have been extensively studied in tumors and are known to play critical roles in tumorigenesis. However, the patterns and origin of pSNMs in normal organs of healthy humans remain largely unknown. Using whole-genome sequencing and ultra-deep amplicon re-sequencing, we identified and validated 164 pSNMs from 27 postmortem organ samples obtained from five healthy donors. The mutant allele fractions ranged from 1.0% to 29.7%. Inter- and intra-organ comparison revealed two distinctive types of pSNMs, with about half originating during early embryogenesis (embryonic pSNMs) and the remaining more likely to result from clonal expansion events that had occurred more recently (clonal expansion pSNMs)...
May 15, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29757144/computational-prediction-of-ctcf-cohesin-based-intra-tad-loops-that-insulate-chromatin-contacts-and-gene-expression-in-mouse-liver
#3
Bryan J Matthews, David J Waxman
CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues...
May 14, 2018: ELife
https://www.readbyqxmd.com/read/29738832/topology-of-interaction-between-titin-and-myosin-thick-filaments
#4
Miklós Kellermayer, Dominik Sziklai, Zsombor Papp, Brennan Decker, Eszter Lakatos, Zsolt Mártonfalvi
Titin is a giant protein spanning between the Z- and M-lines of the sarcomere. In the A-band titin is associated with the myosin thick filament. It has been speculated that titin may serve as a blueprint for thick-filament formation due to the super-repeat structure of its A-band domains. Accordingly, titin might provide a template that determines the length and structural periodicity of the thick filament. Here we tested the titin ruler hypothesis by mixing titin and myosin at in situ stoichiometric ratios (300 myosins per 12 titins) in buffers of different ionic strength (KCl concentration range 100-300 mM)...
May 5, 2018: Journal of Structural Biology
https://www.readbyqxmd.com/read/29729833/compaction-of-single-molecule-megabase-long-chromatin-under-the-influence-of-macromolecular-crowding
#5
Anatoly Zinchenko, Nikolay V Berezhnoy, Qinming Chen, Lars Nordenskiöld
The megabase-sized length of chromatin is highly relevant to the state of chromatin in vivo, where it is subject to a highly crowded environment and is organized in topologically associating domains of similar dimension. We developed an in vitro experimental chromatin model system reconstituted from T4 DNA (approximately 166 kbp) and histone octamers and studied the monomolecular compaction of this megabase-sized chromatin fiber under the influence of macromolecular crowding. We used single-molecule fluorescence microscopy and observed compaction in aqueous solutions containing poly(ethylene glycol) in the presence of monovalent (Na+ and K+ ) and divalent (Mg2+ ) cations...
May 2, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29728659/topologically-knotted-deubiquitinases-exhibit-unprecedented-mechanostability-to-withstand-the-proteolysis-by-an-aaa-protease
#6
Manoj Kumar Sriramoju, Yen Chen, Yun-Tzai Cloud Lee, Shang-Te Danny Hsu
More than one thousand knotted protein structures have been identified so far, but the functional roles of these knots remain elusive. It has been postulated that backbone entanglement may provide additional mechanostability. Here, we employed a bacterial proteasome, ClpXP, to mechanically unfold 52 -knotted human ubiquitin C-terminal hydrolase (UCH) paralogs from their C-termini, followed by processive translocation into the proteolytic chamber for degradation. Our results revealed unprecedentedly slow kinetics of ClpXP-mediated proteolysis for the proteasome-associated UCHL5: ten thousand times slower than that of a green fluorescence protein (GFP), which has a comparable size to the UCH domain but much higher chemical and thermal stabilities...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29724824/distinctive-phosphoinositide-and-ca-2-binding-properties-of-normal-and-cognitive-performance-linked-variant-forms-of-kibra-c2-domain
#7
Mareike G Posner, Abhishek Upadhyay, Rieko Ishima, Antreas C Kalli, Gemma Harris, Joachim Kremerskothen, Mark S P Sansom, Susan J Crennell, Stefan Bagby
KIBRA, a multi-functional scaffold protein with around twenty known binding partners, is involved in memory and cognition, organ size control via the Hippo pathway, cell polarity, and membrane trafficking. KIBRA includes tandem N-terminal WW domains, a C2 domain and motifs for binding aPKC and PDZ domains. A naturally occurring human KIBRA variant involving residue changes at positions 734 (M-to-I) and 735 (S-to-A) within the C2 domain affects cognitive performance. We have elucidated 3D structures, and calcium and phosphoinositide binding properties, of human KIBRA C2 domain...
May 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29713370/sov_refine-a-further-refined-definition-of-segment-overlap-score-and-its-significance-for-protein-structure-similarity
#8
Tong Liu, Zheng Wang
Background: The segment overlap score (SOV) has been used to evaluate the predicted protein secondary structures, a sequence composed of helix (H), strand (E), and coil (C), by comparing it with the native or reference secondary structures, another sequence of H, E, and C. SOV's advantage is that it can consider the size of continuous overlapping segments and assign extra allowance to longer continuous overlapping segments instead of only judging from the percentage of overlapping individual positions as Q3 score does...
2018: Source Code for Biology and Medicine
https://www.readbyqxmd.com/read/29700484/computational-3d-genome-modeling-using-chrom3d
#9
Jonas Paulsen, Tharvesh Moideen Liyakat Ali, Philippe Collas
Chrom3D is a computational platform for 3D genome modeling that simulates the spatial positioning of chromosome domains relative to each other and relative to the nuclear periphery. In Chrom3D, chromosomes are modeled as chains of contiguous beads, in which each bead represents a genomic domain. In this protocol, a bead represents a topologically associated domain (TAD) mapped from ensemble Hi-C data. Chrom3D takes as input data significant pairwise TAD-TAD interactions determined from a Hi-C contact matrix, and TAD interactions with the nuclear periphery, determined by ChIP-sequencing of nuclear lamins to define lamina-associated domains (LADs)...
May 2018: Nature Protocols
https://www.readbyqxmd.com/read/29696806/association-of-17q24-2-q24-3-deletions-with-recognizable-phenotype-and-short-telomeres
#10
Miroslava Hancarova, Marcela Malikova, Michaela Kotrova, Jana Drabova, Marie Trkova, Zdenek Sedlacek
Microdeletions of 17q24.2-q24.3 have been described in several patients with developmental and speech delay, growth retardation, and other features. The relatively large size and limited overlap of the deletions complicate the genotype-phenotype correlation. We identified a girl with intellectual disability, growth retardation, dysmorphic features, and a de novo 2.8 Mb long deletion of 17q24.2-q24.3. Her phenotype was strikingly similar to one previously described boy with Dubowitz syndrome (MIM 223370) and a de novo 3...
April 25, 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29692413/structural-variation-in-the-3d-genome
#11
REVIEW
Malte Spielmann, Darío G Lupiáñez, Stefan Mundlos
Structural and quantitative chromosomal rearrangements, collectively referred to as structural variation (SV), contribute to a large extent to the genetic diversity of the human genome and thus are of high relevance for cancer genetics, rare diseases and evolutionary genetics. Recent studies have shown that SVs can not only affect gene dosage but also modulate basic mechanisms of gene regulation. SVs can alter the copy number of regulatory elements or modify the 3D genome by disrupting higher-order chromatin organization such as topologically associating domains...
April 24, 2018: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/29690904/ocean-c-mapping-hubs-of-open-chromatin-interactions-across-the-genome-reveals-gene-regulatory-networks
#12
Tingting Li, Lumeng Jia, Yong Cao, Qing Chen, Cheng Li
We develop a method called open chromatin enrichment and network Hi-C (OCEAN-C) for antibody-independent mapping of global open chromatin interactions. By integrating FAIRE-seq and Hi-C, OCEAN-C detects open chromatin interactions enriched by active cis-regulatory elements. We identify more than 10,000 hubs of open chromatin interactions (HOCIs) in human cells, which are mainly active promoters and enhancers bound by many DNA-binding proteins and form interaction networks crucial for gene transcription. In addition to identifying large-scale topological structures, including topologically associated domains and A/B compartments, OCEAN-C can detect HOCI-mediated chromatin interactions that are strongly associated with gene expression, super-enhancers, and broad H3K4me3 domains...
April 24, 2018: Genome Biology
https://www.readbyqxmd.com/read/29686034/topologically-associating-domains-in-chromosome-architecture-and-gene-regulatory-landscapes-during-development-disease-and-evolution
#13
Rafael Galupa, Edith Heard
The packaging of genetic material into chromatin and chromosomes has been recognized for more than a century, thanks to microscopy and biochemical approaches. This was followed by the progressive realization that chromatin organization is critical for genome functions such as transcription and DNA replication and repair. The recent discovery that chromosomes are partitioned at the submegabase scale into topologically associating domains (TADs) has implications for our understanding of gene regulation during developmental processes such as X-chromosome inactivation, as well as for evolution and for the search for disease-associated loci...
April 23, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29678937/identification-of-a-specific-functional-network-altered-in-poststroke-cognitive-impairment
#14
Clément Bournonville, Hilde Hénon, Thibaut Dondaine, Christine Delmaire, Stephanie Bombois, Anne-Marie Mendyk, Charlotte Cordonnier, Solène Moulin, Xavier Leclerc, Régis Bordet, Renaud Lopes
OBJECTIVE: To study the association between poststroke cognitive impairment and defining a specific resting functional marker. METHODS: The resting-state functional connectivity 6 months after an ischemic stroke in 56 patients was investigated. Twenty-nine of the patients who had an impairment of one or several cognitive domains were compared to 27 without any cognitive deficit. We studied the whole-brain connectivity using 2 complementary approaches: graph theory to study the functional network organization and network-based statistics to explore connectivity between brain regions...
April 20, 2018: Neurology
https://www.readbyqxmd.com/read/29674479/regionally-clustered-abcc8-polymorphisms-in-a-prospective-cohort-predict-cerebral-oedema-and-outcome-in-severe-traumatic-brain-injury
#15
Ruchira Menka Jha, Theresa A Koleck, Ava M Puccio, David O Okonkwo, Seo-Young Park, Benjamin E Zusman, Robert S B Clark, Lori A Shutter, Jessica S Wallisch, Philip E Empey, Patrick M Kochanek, Yvette P Conley
OBJECTIVE: ABCC8 encodes sulfonylurea receptor 1, a key regulatory protein of cerebral oedema in many neurological disorders including traumatic brain injury (TBI). Sulfonylurea-receptor-1 inhibition has been promising in ameliorating cerebral oedema in clinical trials. We evaluated whether ABCC8 tag single-nucleotide polymorphisms predicted oedema and outcome in TBI. METHODS: DNA was extracted from 485 prospectively enrolled patients with severe TBI. 410 were analysed after quality control...
April 19, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29674002/dengue-virus-ns2-and-ns4-minor-proteins-mammoth-roles
#16
REVIEW
Sindhoora Bhargavi Gopala Reddy, Wei-Xin Chin, Nanjunda Swamy Shivananju
Despite the ever increasing global incidence of dengue fever, there are no specific chemotherapy regimens for its treatment. Structural studies on dengue virus (DENV) proteins have revealed potential drug targets. Major DENV proteins such as the envelope protein and non-structural (NS) proteins 3 and 5 have been extensively investigated in antiviral studies, but with limited success in vitro. However, the minor NS proteins NS2 and NS4 have remained relatively underreported. Emerging evidence indicating their indispensable roles in virus propagation and host immunomodulation should encourage us to target these proteins for drug discovery...
April 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29662163/polymer-physics-predicts-the-effects-of-structural-variants-on-chromatin-architecture
#17
Simona Bianco, Darío G Lupiáñez, Andrea M Chiariello, Carlo Annunziatella, Katerina Kraft, Robert Schöpflin, Lars Wittler, Guillaume Andrey, Martin Vingron, Ana Pombo, Stefan Mundlos, Mario Nicodemi
Structural variants (SVs) can result in changes in gene expression due to abnormal chromatin folding and cause disease. However, the prediction of such effects remains a challenge. Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts...
April 16, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29660196/genome-wide-hi-c-analysis-reveals-extensive-hierarchical-chromatin-interactions-in-rice
#18
Qianli Dong, Ning Li, Xiaochong Li, Zan Yuan, Dejian Xie, Xiaofei Wang, Jianing Li, Yanan Yu, Jinbin Wang, Baoxu Ding, Zhibin Zhang, Changping Li, Yao Bian, Ai Zhang, Ying Wu, Bao Liu, Lei Gong
The non-random spatial packing of chromosomes in the nucleus plays critical roles in orchestrating gene expression and genome function. Here, we present a Hi-C analysis of the chromatin interaction patterns in rice (Oryza sativa L.) at hierarchical architectural levels. We confirm that rice chromosomes occupy their own territories with certain preferential inter-chromosomal associations. Moderate compartment delimitation and extensive TADs (Topologically Associated Domains) were determined to be associated with heterogeneous genomic compositions and epigenetic marks in the rice genome...
April 16, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29659604/similarity-in-replication-timing-between-polytene-and-diploid-cells-is-associated-with-the-organization-of-the-drosophila-genome
#19
Tatyana D Kolesnikova, Fedor P Goncharov, Igor F Zhimulev
Morphologically, polytene chromosomes of Drosophila melanogaster consist of compact "black" bands alternating with less compact "grey" bands and interbands. We developed a comprehensive approach that combines cytological mapping data of FlyBase-annotated genes and novel tools for predicting cytogenetic features of chromosomes on the basis of their protein composition and determined the genomic coordinates for all black bands of polytene chromosome 2R. By a PCNA immunostaining assay, we obtained the replication timetable for all the bands mapped...
2018: PloS One
https://www.readbyqxmd.com/read/29657132/structure-of-radical-induced-cell-death1-hub-domain-reveals-a-common-%C3%AE-%C3%AE-scaffold-for-disorder-in-transcriptional-networks
#20
Katrine Bugge, Lasse Staby, Katherine R Kemplen, Charlotte O'Shea, Sidsel K Bendsen, Mikael K Jensen, Johan G Olsen, Karen Skriver, Birthe B Kragelund
Communication within cells relies on a few protein nodes called hubs, which organize vast interactomes with many partners. Frequently, hub proteins are intrinsically disordered conferring multi-specificity and dynamic communication. Conversely, folded hub proteins may organize networks using disordered partners. In this work, the structure of the RST domain, a unique folded hub, is solved by nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, and its complex with a region of the transcription factor DREB2A is provided through data-driven HADDOCK modeling and mutagenesis analysis...
April 12, 2018: Structure
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