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topologically associated domains

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https://www.readbyqxmd.com/read/29140466/transcription-induced-supercoiling-as-the-driving-force-of-chromatin-loop-extrusion-during-formation-of-tads-in-interphase-chromosomes
#1
Dusan Racko, Fabrizio Benedetti, Julien Dorier, Andrzej Stasiak
Using molecular dynamics simulations, we show here that growing plectonemes resulting from transcription-induced supercoiling have the ability to actively push cohesin rings along chromatin fibres. The pushing direction is such that within each topologically associating domain (TAD) cohesin rings forming handcuffs move from the source of supercoiling, constituted by RNA polymerase with associated DNA topoisomerase TOP1, towards borders of TADs, where supercoiling is released by topoisomerase TOPIIB. Cohesin handcuffs are pushed by continuous flux of supercoiling that is generated by transcription and is then progressively released by action of TOPIIB located at TADs borders...
November 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29139161/cognitive-abilities-brain-white-matter-hyperintensity-volume-and-structural-network-connectivity-in-older-age
#2
Stewart J Wiseman, Tom Booth, Stuart J Ritchie, Simon R Cox, Susana Muñoz Maniega, Maria Del C Valdés Hernández, David Alexander Dickie, Natalie A Royle, John M Starr, Ian J Deary, Joanna M Wardlaw, Mark E Bastin
OBJECTIVE: To assess brain structural connectivity in relation to cognitive abilities in healthy ageing, and the mediating effects of white matter hyper-intensity (WMH) volume. METHODS: MRI data were analysed in 558 members of the Lothian Birth Cohort 1936. Brains were segmented into 85 regions and combined with tractography to generate structural connectomes. WMH volume was quantified. Relationships between whole-brain connectivity, assessed using graph theory metrics, and four major domains of cognitive ability (visuospatial reasoning, verbal memory, information processing speed and crystallized ability) were investigated, as was the mediating effects of WMH volume on these relationships...
November 14, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/29137603/clustertad-an-unsupervised-machine-learning-approach-to-detecting-topologically-associated-domains-of-chromosomes-from-hi-c-data
#3
Oluwatosin Oluwadare, Jianlin Cheng
BACKGROUND: With the development of chromosomal conformation capturing techniques, particularly, the Hi-C technique, the study of the spatial conformation of a genome is becoming an important topic in bioinformatics and computational biology. The Hi-C technique can generate genome-wide chromosomal interaction (contact) data, which can be used to investigate the higher-level organization of chromosomes, such as Topologically Associated Domains (TAD), i.e., locally packed chromosome regions bounded together by intra chromosomal contacts...
November 14, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29133252/l-rhamnose-binding-lectins-rbls-in-nile-tilapia-oreochromis-niloticus-characterization-and-expression-profiling-in-mucosal-tissues
#4
Dongdong Zhang, Benjamin H Beck, Haitham Mohammed, Honggang Zhao, Wilawan Thongda, Zhi Ye, Qifan Zeng, Craig Shoemaker, S Adam Fuller, Eric Peatman
Rhamnose-binding lectins (RBLs) are crucial elements associated with innate immune responses to infections and have been characterized from a variety of teleost fishes. Given the importance of RBL in teleost fishes, we sought to study the diversity and expression profiles of RBLs in an important cultured fish, Nile tilapia (Oreochromis niloticus) following experimental infection with Streptococcus agalactiae, a major cause of streptococcosis in farmed tilapia. In this study, four predicted RBL genes were identified from Nile tilapia and were designated as OnRBL3a, OnRBL3b, OnRBL3c, and OnRBL3d...
November 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29126902/identification-and-characterization-of-the-mitochondrial-membrane-sorting-signals-in-phosphatidylserine-decarboxylase-1-from-saccharomyces-cerevisiae
#5
Ariane Wagner, Francesca Di Bartolomeo, Isabella Klein, Claudia Hrastnik, Kim Nguyen Doan, Thomas Becker, Günther Daum
Phosphatidylserine decarboxylase 1 (Psd1p) catalyzes the formation of the majority of phosphatidylethanolamine (PE) in the yeast Saccharomyces cerevisiae. Psd1p is localized to mitochondria, anchored to the inner mitochondrial membrane (IMM) through membrane spanning domains and oriented towards the mitochondrial intermembrane space. We found that Psd1p harbors at least two inner membrane-associated domains, which we named IM1 and IM2. IM1 is important for proper orientation of Psd1p within the IMM (Horvath et al...
November 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29121339/conserved-non-coding-elements-developmental-gene-regulation-meets-genome-organization
#6
Dimitris Polychronopoulos, James W D King, Alexander J Nash, Ge Tan, Boris Lenhard
Comparative genomics has revealed a class of non-protein-coding genomic sequences that display an extraordinary degree of conservation between two or more organisms, regularly exceeding that found within protein-coding exons. These elements, collectively referred to as conserved non-coding elements (CNEs), are non-randomly distributed across chromosomes and tend to cluster in the vicinity of genes with regulatory roles in multicellular development and differentiation. CNEs are organized into functional ensembles called genomic regulatory blocks-dense clusters of elements that collectively coordinate the expression of shared target genes, and whose span in many cases coincides with topologically associated domains...
November 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29112723/in-vitro-and-in-vivo-studies-of-the-als-ftld-protein-chchd10-reveal-novel-mitochondrial-topology-and-protein-interactions
#7
S R Burstein, F Valsecchi, H Kawamata, M Bourens, R Zeng, A Zuberi, T A Milner, S M Cloonan, C Lutz, A Barrientos, G Manfredi
Mutations in coiled-coil-helix-coiled-coil-helix-domain containing 10 (CHCHD10), a mitochondrial twin CX9C protein whose function is still unknown, cause myopathy, motor neuron disease, frontotemporal dementia, and Parkinson's disease. Here, we investigate CHCHD10 topology and its protein interactome, as well as the effects of CHCHD10 depletion or expression of disease-associated mutations in wild-type cells. We find that CHCHD10 associates with membranes in the mitochondrial intermembrane space, where it interacts with a closely related protein, CHCHD2...
November 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29078370/algorithm-for-cellular-reprogramming
#8
Scott Ronquist, Geoff Patterson, Lindsey A Muir, Stephen Lindsly, Haiming Chen, Markus Brown, Max S Wicha, Anthony Bloch, Roger Brockett, Indika Rajapakse
The day we understand the time evolution of subcellular events at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology. With data-guided frameworks we can develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. Here we describe an approach for optimizing the use of transcription factors (TFs) in cellular reprogramming, based on a device commonly used in optimal control...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29077760/membrane-alterations-induced-by-nonstructural-proteins-of-human-norovirus
#9
Sylvie Y Doerflinger, Mirko Cortese, Inés Romero-Brey, Zach Menne, Thibault Tubiana, Christian Schenk, Peter A White, Ralf Bartenschlager, Stéphane Bressanelli, Grant S Hansman, Volker Lohmann
Human noroviruses (huNoV) are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4) variants. The viral nonstructural (NS) proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far about the ultrastructure of these replication organelles or the contribution of individual NS proteins to their biogenesis. We compared the ultrastructural changes induced by expression of norovirus ORF1 polyproteins with those induced upon infection with murine norovirus (MNV)...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29077530/recent-evidence-that-tads-and-chromatin-loops-are-dynamic-structures
#10
Anders S Hansen, Claudia Cattoglio, Xavier Darzacq, Robert Tjian
Mammalian genomes are folded into spatial domains, which regulate gene expression by modulating enhancer-promoter contacts. Here, we review recent studies on the structure and function of Topologically Associating Domains (TADs) and chromatin loops. We discuss how loop extrusion models can explain TAD formation and evidence that TADs are formed by the ring-shaped protein complex, cohesin, and that TAD boundaries are established by the DNA-binding protein, CTCF. We discuss our recent genomic, biochemical and single-molecule imaging studies on CTCF and cohesin, which suggest that TADs and chromatin loops are dynamic structures...
October 27, 2017: Nucleus
https://www.readbyqxmd.com/read/29073019/structure-and-dynamics-of-the-rnapii-ctdsome-with-rtt103
#11
Olga Jasnovidova, Tomas Klumpler, Karel Kubicek, Sergei Kalynych, Pavel Plevka, Richard Stefl
RNA polymerase II contains a long C-terminal domain (CTD) that regulates interactions at the site of transcription. The CTD architecture remains poorly understood due to its low sequence complexity, dynamic phosphorylation patterns, and structural variability. We used integrative structural biology to visualize the architecture of the CTD in complex with Rtt103, a 3'-end RNA-processing and transcription termination factor. Rtt103 forms homodimers via its long coiled-coil domain and associates densely on the repetitive sequence of the phosphorylated CTD via its N-terminal CTD-interacting domain...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29069428/gelsolin-pathogenic-gly167arg-mutation-promotes-domain-swap-dimerization-of-the-protein
#12
Francesco Bonì, Mario Milani, Alberto Barbiroli, Luisa Diomede, Eloise Mastrangelo, Matteo de Rosa
AGel amyloidosis is a genetic degenerative disease characterized by the deposition of insoluble gelsolin protein aggregates in different tissues. Until recently, this disease was associated with two mutations of a single residue (Asp187 to Asn/Tyr) in the second domain of the protein. The general opinion is that pathogenic variants are not per se amyloidogenic but rather that the mutations trigger an aberrant proteolytic cascade, which results in the production of aggregation prone fragments. Here we report the crystal structure of the second domain of gelsolin carrying the recently identified Gly167Arg mutation...
October 23, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29042628/a-dna-contact-map-for-the-mouse-runx1-gene-identifies-novel-haematopoietic-enhancers
#13
Judith Marsman, Amarni Thomas, Motomi Osato, Justin M O'Sullivan, Julia A Horsfield
The transcription factor Runx1 is essential for definitive haematopoiesis, and the RUNX1 gene is frequently translocated or mutated in leukaemia. Runx1 is transcribed from two promoters, P1 and P2, to give rise to different protein isoforms. Although the expression of Runx1 must be tightly regulated for normal blood development, the mechanisms that regulate Runx1 isoform expression during haematopoiesis remain poorly understood. Gene regulatory elements located in non-coding DNA are likely to be important for Runx1 transcription...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29034683/a-budding-defective-m2-mutant-exhibits-reduced-membrane-interaction-insensitivity-to-cholesterol-and-perturbed-interdomain-coupling
#14
Alice L Herneisen, Indra D Sahu, Robert M McCarrick, Jimmy B Feix, Gary A Lorigan, Kathleen P Howard
Influenza A M2 is a membrane-associated protein with a C-terminal amphipathic helix that plays a cholesterol-dependent role in viral budding. An M2 mutant with alanine substitutions in the C-terminal amphipathic helix is deficient in viral scission. With the goal of providing atomic-level understanding of how the wild-type protein functions, we used a multipronged site-directed spin labeling electron paramagnetic resonance spectroscopy (SDSL-EPR) approach to characterize the conformational properties of the alanine mutant...
October 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/29025761/genome-wide-association-study-to-find-modifiers-for-tetralogy-of-fallot-in-the-22q11-2-deletion-syndrome-identifies-variants-in-the-gpr98-locus-on-5q14-3
#15
Tingwei Guo, Gabriela M Repetto, Donna M McDonald McGinn, Jonathan H Chung, Hiroko Nomaru, Christopher L Campbell, Anna Blonska, Anne S Bassett, Eva W C Chow, Elisabeth E Mlynarski, Ann Swillen, Joris Vermeesch, Koen Devriendt, Doron Gothelf, Miri Carmel, Elena Michaelovsky, Maude Schneider, Stephan Eliez, Stylianos E Antonarakis, Karlene Coleman, Aoy Tomita-Mitchell, Michael E Mitchell, M Cristina Digilio, Bruno Dallapiccola, Bruno Marino, Nicole Philip, Tiffany Busa, Leila Kushan-Wells, Carrie E Bearden, Małgorzata Piotrowicz, Wanda Hawuła, Amy E Roberts, Flora Tassone, Tony J Simon, Esther D A van Duin, Thérèse A van Amelsvoort, Wendy R Kates, Elaine Zackai, H Richard Johnston, David J Cutler, A J Agopian, Elizabeth Goldmuntz, Laura E Mitchell, Tao Wang, Beverly S Emanuel, Bernice E Morrow
BACKGROUND: The 22q11.2 deletion syndrome (22q11.2DS; DiGeorge syndrome/velocardiofacial syndrome) occurs in 1 of 4000 live births, and 60% to 70% of affected individuals have congenital heart disease, ranging from mild to severe. In our cohort of 1472 subjects with 22q11.2DS, a total of 62% (n=906) have congenital heart disease and 36% (n=326) of these have tetralogy of Fallot (TOF), comprising the largest subset of severe congenital heart disease in the cohort. METHODS AND RESULTS: To identify common genetic variants associated with TOF in individuals with 22q11...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28991264/architectural-alterations-of-the-fission-yeast-genome-during-the-cell-cycle
#16
Hideki Tanizawa, Kyoung-Dong Kim, Osamu Iwasaki, Ken-Ichi Noma
Eukaryotic genomes are highly ordered through various mechanisms, including topologically associating domain (TAD) organization. We employed an in situ Hi-C approach to follow the 3D organization of the fission yeast genome during the cell cycle. We demonstrate that during mitosis, large domains of 300 kb-1 Mb are formed by condensin. This mitotic domain organization does not suddenly dissolve, but gradually diminishes until the next mitosis. By contrast, small domains of 30-40 kb that are formed by cohesin are relatively stable across the cell cycle...
November 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28988457/re-evaluating-pathogenicity-of-variants-associated-with-the-long-qt-syndrome
#17
Jonathan R Kaltman, Frank Evans, Yi-Ping Fu
INTRODUCTION: Genetic testing for congenital long-QT syndrome (LQTS) has become common. Recent studies have shown that some variants labelled as pathogenic might be misclassified due to sparse case reports and relatively common allele frequencies in the general population. This study aims to evaluate the presence of LQTS-associated variants in the Genome Aggregation Database (gnomAD) population, and assess the functional impact of these variants. METHODS AND RESULTS: Variants associated with LQTS from the Human Gene Mutation Database were extracted and matched to the gnomAD to evaluate population-based allele frequencies (AF)...
October 8, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/28977568/computational-characterization-of-chromatin-domain-boundary-associated-genomic-elements
#18
Seungpyo Hong, Dongsup Kim
Topologically associated domains (TADs) are 3D genomic structures with high internal interactions that play important roles in genome compaction and gene regulation. Their genomic locations and their association with CCCTC-binding factor (CTCF)-binding sites and transcription start sites (TSSs) were recently reported. However, the relationship between TADs and other genomic elements has not been systematically evaluated. This was addressed in the present study, with a focus on the enrichment of these genomic elements and their ability to predict the TAD boundary region...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28977529/hitad-detecting-the-structural-and-functional-hierarchies-of-topologically-associating-domains-from-chromatin-interactions
#19
Xiao-Tao Wang, Wang Cui, Cheng Peng
A current question in the high-order organization of chromatin is whether topologically associating domains (TADs) are distinct from other hierarchical chromatin domains. However, due to the unclear TAD definition in tradition, the structural and functional uniqueness of TAD is not well studied. In this work, we refined TAD definition by further constraining TADs to the optimal separation on global intra-chromosomal interactions. Inspired by this constraint, we developed a novel method, called HiTAD, to detect hierarchical TADs from Hi-C chromatin interactions...
August 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28977418/developmentally-regulated-higher-order-chromatin-interactions-orchestrate-b-cell-fate-commitment
#20
Ravi Boya, Anurupa Devi Yadavalli, Sameena Nikhat, Sreenivasulu Kurukuti, Dasaradhi Palakodeti, Jagan M R Pongubala
Genome organization in 3D nuclear-space is important for regulation of gene expression. However, the alterations of chromatin architecture that impinge on the B cell-fate choice of multi-potent progenitors are still unclear. By integrating in situ Hi-C analyses with epigenetic landscapes and genome-wide expression profiles, we tracked the changes in genome architecture as the cells transit from a progenitor to a committed state. We identified the genomic loci that undergo developmental switch between A and B compartments during B-cell fate determination...
August 17, 2017: Nucleic Acids Research
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