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topologically associated domains

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https://www.readbyqxmd.com/read/28712921/selective-regulation-of-biological-processes-by-vitamin-d-based-on-the-spatio-temporal-cistrome-of-its-receptor
#1
Antonio Neme, Sabine Seuter, Carsten Carlberg
The transcription factor vitamin D receptor (VDR) is the exclusive nuclear target of the biologically active form of vitamin D (1,25(OH)2D3). In THP-1 human monocytes we obtained a highly accurate VDR cistrome after 2 and 24 h ligand stimulation comprising more than 11,600 genomic loci, 78% of which were detected exclusively after 24 h. In contrast, a group of 510 persistent VDR sites occurred at all conditions and some 2,100 VDR loci were only transiently occupied. Machine learning and statistical analysis as well as a comparison with the re-analyzed B cell VDR cistrome indicated a subgroup of 339 highly conserved persistent VDR sites that were suited best for describing vitamin D-triggered gene regulatory scenarios...
July 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28709003/3d-chromatin-structures-of-mature-gametes-and-structural-reprogramming-during-mammalian-embryogenesis
#2
Yuwen Ke, Yanan Xu, Xuepeng Chen, Songjie Feng, Zhenbo Liu, Yaoyu Sun, Xuelong Yao, Fangzhen Li, Wei Zhu, Lei Gao, Haojie Chen, Zhenhai Du, Wei Xie, Xiaocui Xu, Xingxu Huang, Jiang Liu
High-order chromatin structure plays important roles in gene expression regulation. Knowledge of the dynamics of 3D chromatin structures during mammalian embryo development remains limited. We report the 3D chromatin architecture of mouse gametes and early embryos using an optimized Hi-C method with low-cell samples. We find that mature oocytes at the metaphase II stage do not have topologically associated domains (TADs). In sperm, extra-long-range interactions (>4 Mb) and interchromosomal interactions occur frequently...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28703188/allelic-reprogramming-of-3d-chromatin-architecture-during-early-mammalian-development
#3
Zhenhai Du, Hui Zheng, Bo Huang, Rui Ma, Jingyi Wu, Xianglin Zhang, Jing He, Yunlong Xiang, Qiujun Wang, Yuanyuan Li, Jing Ma, Xu Zhang, Ke Zhang, Yang Wang, Michael Q Zhang, Juntao Gao, Jesse R Dixon, Xiaowo Wang, Jianyang Zeng, Wei Xie
In mammals, chromatin organization undergoes drastic reprogramming after fertilization. However, the three-dimensional structure of chromatin and its reprogramming in preimplantation development remain poorly understood. Here, by developing a low-input Hi-C (genome-wide chromosome conformation capture) approach, we examined the reprogramming of chromatin organization during early development in mice. We found that oocytes in metaphase II show homogeneous chromatin folding that lacks detectable topologically associating domains (TADs) and chromatin compartments...
July 12, 2017: Nature
https://www.readbyqxmd.com/read/28693562/activation-of-the-alpha-globin-gene-expression-correlates-with-dramatic-upregulation-of-nearby-non-globin-genes-and-changes-in-local-and-large-scale-chromatin-spatial-structure
#4
Sergey V Ulianov, Aleksandra A Galitsyna, Ilya M Flyamer, Arkadiy K Golov, Ekaterina E Khrameeva, Maxim V Imakaev, Nezar A Abdennur, Mikhail S Gelfand, Alexey A Gavrilov, Sergey V Razin
BACKGROUND: In homeotherms, the alpha-globin gene clusters are located within permanently open genome regions enriched in housekeeping genes. Terminal erythroid differentiation results in dramatic upregulation of alpha-globin genes making their expression comparable to the rRNA transcriptional output. Little is known about the influence of the erythroid-specific alpha-globin gene transcription outburst on adjacent, widely expressed genes and large-scale chromatin organization. Here, we have analyzed the total transcription output, the overall chromatin contact profile, and CTCF binding within the 2...
July 11, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28691095/condensin-ii-is-anchored-by-tfiiic-and-h3k4me3-in-the-mammalian-genome-and-supports-the-expression-of-active-dense-gene-clusters
#5
Kobe C Yuen, Brian D Slaughter, Jennifer L Gerton
Structural maintenance of chromosome complexes, such as cohesin, have been implicated in a wide variety of chromatin-dependent functions such as genome organization, replication, and gene expression. How these complexes find their sites of association and affect local chromosomal processes is not well understood. We report that condensin II, a complex distinct from cohesin, physically interacts with TFIIIC, and they both colocalize at active gene promoters in the mouse and human genomes, facilitated by interaction between NCAPD3 and the epigenetic mark H3K4me3...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28682332/cell-cycle-dynamics-of-chromosomal-organization-at-single-cell-resolution
#6
Takashi Nagano, Yaniv Lubling, Csilla Várnai, Carmel Dudley, Wing Leung, Yael Baran, Netta Mendelson Cohen, Steven Wingett, Peter Fraser, Amos Tanay
Chromosomes in proliferating metazoan cells undergo marked structural metamorphoses every cell cycle, alternating between highly condensed mitotic structures that facilitate chromosome segregation, and decondensed interphase structures that accommodate transcription, gene silencing and DNA replication. Here we use single-cell Hi-C (high-resolution chromosome conformation capture) analysis to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle...
July 5, 2017: Nature
https://www.readbyqxmd.com/read/28671686/the-methyltransferase-setdb1-regulates-a-large-neuron-specific-topological-chromatin-domain
#7
Yan Jiang, Yong-Hwee Eddie Loh, Prashanth Rajarajan, Teruyoshi Hirayama, Will Liao, Bibi S Kassim, Behnam Javidfar, Brigham J Hartley, Lisa Kleofas, Royce B Park, Benoit Labonte, Seok-Man Ho, Sandhya Chandrasekaran, Catherine Do, Brianna R Ramirez, Cyril J Peter, Julia T C W, Brian M Safaie, Hirofumi Morishita, Panos Roussos, Eric J Nestler, Anne Schaefer, Benjamin Tycko, Kristen J Brennand, Takeshi Yagi, Li Shen, Schahram Akbarian
We report locus-specific disintegration of megabase-scale chromosomal conformations in brain after neuronal ablation of Setdb1 (also known as Kmt1e; encodes a histone H3 lysine 9 methyltransferase), including a large topologically associated 1.2-Mb domain conserved in humans and mice that encompasses >70 genes at the clustered protocadherin locus (hereafter referred to as cPcdh). The cPcdh topologically associated domain (TAD(cPcdh)) in neurons from mutant mice showed abnormal accumulation of the transcriptional regulator and three-dimensional (3D) genome organizer CTCF at cryptic binding sites, in conjunction with DNA cytosine hypomethylation, histone hyperacetylation and upregulated expression...
July 3, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28662178/genetic-association-of-fto-irx-region-with-obesity-and-overweight-in-the-polish-population
#8
Marta Sobalska-Kwapis, Aleksandra Suchanecka, Marcin Słomka, Anna Siewierska-Górska, Ewa Kępka, Dominik Strapagiel
BACKGROUND/OBJECTIVES: Genome-wide association studies (GWAS) have identified many loci associated with body mass index (BMI) in many different populations. Variants in the FTO locus are reported to be one of the strongest genetic predictors of obesity. Recent publications pointed also to a topologically associated domain (TAD) which is identified as a novel region affecting BMI. The TAD area encompasses the IRXB cluster (IRX3, IRX5, IRX6), FTO and RPGRIP1L genes. SUBJECTS/METHODS: In this study, we investigated the relationship between variation of the FTO and IRX genes and obesity in Poles...
2017: PloS One
https://www.readbyqxmd.com/read/28646141/human-sialidase-neu3-is-s-acylated-and-behaves-like-an-integral-membrane-protein
#9
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
#10
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
#11
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
#12
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
#13
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...
July 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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 2 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 2 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
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