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https://www.readbyqxmd.com/read/28167501/comprehensive-characterization-of-neutrophil-genome-topology
#1
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...
February 6, 2017: Genes & Development
https://www.readbyqxmd.com/read/28167211/an-insight-into-the-orphan-nucleotide-sugar-transporter-slc35a4
#2
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...
February 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28157505/polycomb-repressive-complex-1-generates-discrete-compacted-domains-that-change-during-differentiation
#3
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
#4
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
https://www.readbyqxmd.com/read/28137286/chrom3d-three-dimensional-genome-modeling-from-hi-c-and-nuclear-lamin-genome-contacts
#5
Jonas Paulsen, Monika Sekelja, Anja R Oldenburg, Alice Barateau, Nolwenn Briand, Erwan Delbarre, Akshay Shah, Anita L Sørensen, Corinne Vigouroux, Brigitte Buendia, Philippe Collas
Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells...
January 30, 2017: Genome Biology
https://www.readbyqxmd.com/read/28133491/insights-into-genome-architecture-deduced-from-the-properties-of-short-lac-repressor-mediated-dna-loops
#6
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 allows 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/28108933/modelling-genome-wide-topological-associating-domains-in-mouse-embryonic-stem-cells
#7
REVIEW
Y Zhan, L Giorgetti, G Tiana
Chromosome conformation capture (3C)-based techniques such as chromosome conformation capture carbon copy (5C) and Hi-C revealed that the folding of mammalian chromosomes is highly hierarchical. A fundamental structural unit in the hierarchy is represented by topologically associating domains (TADs), sub-megabase regions of the genome within which the chromatin fibre preferentially interacts. 3C-based methods provide the mean contact probabilities between chromosomal loci, averaged over a large number of cells, and do not give immediate access to the single-cell conformations of the chromatin fibre...
January 20, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28099032/pathogenicity-genes-in-ustilaginoidea-virens-revealed-by-a-predicted-protein-protein-interaction-network
#8
Kang Zhang, Yuejiao Li, Tengjiao Li, Zhi-Gang Li, Tom Hsiang, Ziding Zhang, Wenxian Sun
Rice false smut, caused by Ustilaginoidea virens, produces significant losses in rice yield and grain quality and has recently emerged as one of the most important rice diseases worldwide. Despite its importance in rice production, relatively few studies have been conducted to illustrate the complex interactome and the pathogenicity gene interactions. Here a protein-protein interaction network of U. virens was built through two well-recognized approaches, interolog- and domain-domain interaction-based methods...
February 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28091955/genome-wide-exploration-of-silicon-si-transporter-genes-lsi1-and-lsi2-in-plants-insights-into-si-accumulation-status-capacity-of-plants
#9
Recep Vatansever, Ibrahim Ilker Ozyigit, Ertugrul Filiz, Nermin Gozukara
Silicon (Si) is a nonessential, beneficial micronutrient for plants. It increases the plant stress tolerance in relation to its accumulation capacity. In this work, root Si transporter genes were characterized in 17 different plants and inferred for their Si-accumulation status. A total of 62 Si transporter genes (31 Lsi1 and 31 Lsi2) were identified in studied plants. Lsi1s were 261-324 residues protein with a MIP family domain whereas Lsi2s were 472-547 residues with a citrate transporter family domain. Lsi1s possessed characteristic sequence features that can be employed as benchmark in prediction of Si-accumulation status/capacity of the plants...
January 13, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28087711/ctcf-mediated-topological-boundaries-during-development-foster-appropriate-gene-regulation
#10
Varun Narendra, Milica Bulajić, Job Dekker, Esteban O Mazzoni, Danny Reinberg
The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087167/lingering-questions-about-enhancer-rna-and-enhancer-transcription-coupled-genomic-instability
#11
REVIEW
Gerson Rothschild, Uttiya Basu
Intergenic and intragenic enhancers found inside topologically associated regulatory domains (TADs) express noncoding RNAs, known as enhancer RNAs (eRNAs). Recent studies have indicated these eRNAs play a role in gene regulatory networks by controlling promoter and enhancer interactions and topology of higher-order chromatin structure. Misregulation of enhancer and promoter associated noncoding RNAs (ncRNAs) could stabilize deleterious secondary DNA structures, noncoding RNA associated DNA/RNA hybrid formation, and promote collisions of transcription complexes with replisomes...
February 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28076974/topological-organization-of-whole-brain-white-matter-in-hiv-infection
#12
Laurie M Baker, Sarah Cooley, Ryan P Cabeen, David H Laidlaw, John A Joska, Jacqueline Hoare, Dan J Stein, Jodi Heaps-Woodruff, Lauren E Salminen, Robert H Paul
Infection with human immunodeficiency virus (HIV) is associated with neuroimaging alterations. However, little is known about the topological organization of whole-brain networks and the corresponding association with cognition. As such, we examined structural whole-brain white matter connectivity patterns and cognitive performance in 29 HIV+ young adults (mean age = 25.9) with limited or no HIV treatment history. HIV+ participants and demographically similar HIV- controls (n = 16) residing in South Africa underwent magnetic resonance imaging (MRI) and neuropsychological testing...
January 11, 2017: Brain Connectivity
https://www.readbyqxmd.com/read/28070687/predicting-chromatin-architecture-from-models-of-polymer-physics
#13
REVIEW
Simona Bianco, Andrea M Chiariello, Carlo Annunziatella, Andrea Esposito, Mario Nicodemi
We review the picture of chromatin large-scale 3D organization emerging from the analysis of Hi-C data and polymer modeling. In higher mammals, Hi-C contact maps reveal a complex higher-order organization, extending from the sub-Mb to chromosomal scales, hierarchically folded in a structure of domains-within-domains (metaTADs). The domain folding hierarchy is partially conserved throughout differentiation, and deeply correlated to epigenomic features. Rearrangements in the metaTAD topology relate to gene expression modifications: in particular, in neuronal differentiation models, topologically associated domains (TADs) tend to have coherent expression changes within architecturally conserved metaTAD niches...
January 9, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28060840/an-isochore-framework-underlies-chromatin-architecture
#14
Kamel Jabbari, Giorgio Bernardi
A recent investigation showed the existence of correlations between the architectural features of mammalian interphase chromosomes and the compositional properties of isochores. This result prompted us to compare maps of the Topologically Associating Domains (TADs) and of the Lamina Associated Domains (LADs) with the corresponding isochore maps of mouse and human chromosomes. This approach revealed that: 1) TADs and LADs correspond to isochores, i.e., isochores are the genomic units that underlie chromatin domains; 2) the conservation of TADs and LADs in mammalian genomes is explained by the evolutionary conservation of isochores; 3) chromatin domains corresponding to GC-poor isochores (e...
2017: PloS One
https://www.readbyqxmd.com/read/28060558/the-connection-between-brg1-ctcf-and-topoisomerases-at-tad-boundaries
#15
A Rasim Barutcu, Jane B Lian, Janet L Stein, Gary S Stein, Anthony N Imbalzano
The eukaryotic genome is partitioned into topologically associating domains (TADs). Despite recent advances characterizing TADs and TAD boundaries, the organization of these structures is an important dimension of genome architecture and function that is not well understood. Recently, we demonstrated that knockdown of BRG1, an ATPase driving the chromatin remodeling activity of mammalian SWI/SNF enzymes, globally alters long-range genomic interactions and results in a reduction of TAD boundary strength. We provided evidence suggesting that this effect may be due to BRG1 affecting nucleosome occupancy around CTCF sites present at TAD boundaries...
January 6, 2017: Nucleus
https://www.readbyqxmd.com/read/28057745/reciprocal-insulation-analysis-of-hi-c-data-shows-that-tads-represent-a-functionally-but-not-structurally-privileged-scale-in-the-hierarchical-folding-of-chromosomes
#16
Yinxiu Zhan, Luca Mariani, Iros Barozzi, Edda G Schulz, Nils Bluthgen, Michael Stadler, Guido Tiana, Luca Giorgetti
Understanding how regulatory sequences interact in the context of chromosomal architecture is a central challenge in biology. Chromosome conformation capture revealed that mammalian chromosomes possess a rich hierarchy of structural layers, from multi-megabase compartments to sub-megabase topologically associating domains (TADs) and sub-TAD contact domains. TADs appear to act as regulatory microenvironments by constraining and segregating regulatory interactions across discrete chromosomal regions. However, it is unclear whether other (or all) folding layers share similar properties, or rather TADs constitute a privileged folding scale with maximal impact on the organization of regulatory interactions...
January 5, 2017: Genome Research
https://www.readbyqxmd.com/read/28056762/hic-bench-comprehensive-and-reproducible-hi-c-data-analysis-designed-for-parameter-exploration-and-benchmarking
#17
Charalampos Lazaris, Stephen Kelly, Panagiotis Ntziachristos, Iannis Aifantis, Aristotelis Tsirigos
BACKGROUND: Chromatin conformation capture techniques have evolved rapidly over the last few years and have provided new insights into genome organization at an unprecedented resolution. Analysis of Hi-C data is complex and computationally intensive involving multiple tasks and requiring robust quality assessment. This has led to the development of several tools and methods for processing Hi-C data. However, most of the existing tools do not cover all aspects of the analysis and only offer few quality assessment options...
January 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28018208/global-efficiency-of-structural-networks-mediates-cognitive-control-in-mild-cognitive-impairment
#18
Rok Berlot, Claudia Metzler-Baddeley, M Arfan Ikram, Derek K Jones, Michael J O'Sullivan
Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localized white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI). Materials and Methods: Twenty-five patients with MCI and 20 age, sex, and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI)...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27974201/functional-mutations-form-at-ctcf-cohesin-binding-sites-in-melanoma-due-to-uneven-nucleotide-excision-repair-across-the-motif
#19
Rebecca C Poulos, Julie A I Thoms, Yi Fang Guan, Ashwin Unnikrishnan, John E Pimanda, Jason W H Wong
CTCF binding sites are frequently mutated in cancer, but how these mutations accumulate and whether they broadly perturb CTCF binding are not well understood. Here, we report that skin cancers exhibit a highly specific asymmetric mutation pattern within CTCF motifs attributable to ultraviolet irradiation and differential nucleotide excision repair (NER). CTCF binding site mutations form independently of replication timing and are enriched at sites of CTCF/cohesin complex binding, suggesting a role for cohesin in stabilizing CTCF-DNA binding and impairing NER...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27973779/concatemers-of-outer-membrane-protein-a-take-detours-in-the-folding-landscape
#20
Kell K Andersen, Brian Vad, Sahar Omer, Daniel E Otzen
Outer membrane protein A (OmpA) is the most abundant protein in the outer membrane of Escherichia coli. The N-terminal domain forms an eight-stranded membrane-embedded β-barrel that is widely used as a model protein for in vitro folding into the membrane and into surfactant micelles. Under conditions that include a low surfactant concentration, OmpA can form stable higher-order structures by intermolecular association. Other β-barrel membrane proteins also associate to form noncovalently linked trimers in vivo...
December 27, 2016: Biochemistry
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