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topologically associated domains

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https://www.readbyqxmd.com/read/28802249/high-resolution-mapping-of-chromatin-conformation-in-cardiac-myocytes-reveals-structural-remodeling-of-the-epigenome-in-heart-failure
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28780612/invisible-cities-segregated-domains-in-the-yeast-genome-with-distinct-structural-and-functional-attributes
#5
Christoforos Nikolaou
Recent advances in our understanding of the three-dimensional organization of the eukaryotic nucleus have rendered the spatial distribution of genes increasingly relevant. In a recent work (Tsochatzidou et al., Nucleic Acids Res 45:5818-5828, 2017), we proposed the existence of a functional compartmentalization of the yeast genome according to which, genes occupying the chromosomal regions at the nuclear periphery have distinct structural, functional and evolutionary characteristics compared to their centromeric-proximal counterparts...
August 5, 2017: Current Genetics
https://www.readbyqxmd.com/read/28752854/ctcf-fences-make-good-neighbours
#6
Ivan Krivega, Ann Dean
CCCTC-binding factor (CTCF) sites are enriched at the boundaries of topologically associated domains (TADs), but their function within TADs is unclear. Removal of sub-TAD CTCF sites adjacent to the α-globin enhancers is now shown to result in inappropriate activation of neighbouring genes. Intra-TAD enhancer insulation might be broadly important for tissue specificity of enhancers.
July 28, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28742097/mrtadfinder-a-network-modularity-based-approach-to-identify-topologically-associating-domains-in-multiple-resolutions
#7
Koon-Kiu Yan, Shaoke Lou, Mark Gerstein
Genome-wide proximity ligation based assays such as Hi-C have revealed that eukaryotic genomes are organized into structural units called topologically associating domains (TADs). From a visual examination of the chromosomal contact map, however, it is clear that the organization of the domains is not simple or obvious. Instead, TADs exhibit various length scales and, in many cases, a nested arrangement. Here, by exploiting the resemblance between TADs in a chromosomal contact map and densely connected modules in a network, we formulate TAD identification as a network optimization problem and propose an algorithm, MrTADFinder, to identify TADs from intra-chromosomal contact maps...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28737770/tissue-specific-ctcf-cohesin-mediated-chromatin-architecture-delimits-enhancer-interactions-and-function-in-vivo
#8
Lars L P Hanssen, Mira T Kassouf, A Marieke Oudelaar, Daniel Biggs, Chris Preece, Damien J Downes, Matthew Gosden, Jacqueline A Sharpe, Jacqueline A Sloane-Stanley, Jim R Hughes, Benjamin Davies, Douglas R Higgs
The genome is organized via CTCF-cohesin-binding sites, which partition chromosomes into 1-5 megabase (Mb) topologically associated domains (TADs), and further into smaller sub-domains (sub-TADs). Here we examined in vivo an ∼80 kb sub-TAD, containing the mouse α-globin gene cluster, lying within a ∼1 Mb TAD. We find that the sub-TAD is flanked by predominantly convergent CTCF-cohesin sites that are ubiquitously bound by CTCF but only interact during erythropoiesis, defining a self-interacting erythroid compartment...
August 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28737695/predictive-structure-and-topology-of-peroxisomal-atp-binding-cassette-abc-transporters
#9
Pierre Andreoletti, Quentin Raas, Catherine Gondcaille, Mustapha Cherkaoui-Malki, Doriane Trompier, Stéphane Savary
The peroxisomal ATP-binding Cassette (ABC) transporters, which are called ABCD1, ABCD2 and ABCD3, are transmembrane proteins involved in the transport of various lipids that allow their degradation inside the organelle. Defective ABCD1 leads to the accumulation of very long-chain fatty acids and is associated with a complex and severe neurodegenerative disorder called X-linked adrenoleukodystrophy (X-ALD). Although the nucleotide-binding domain is highly conserved and characterized within the ABC transporters family, solid data are missing for the transmembrane domain (TMD) of ABCD proteins...
July 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28722347/foxo3-longevity-interactome-on-chromosome-6
#10
Timothy A Donlon, Brian J Morris, Randi Chen, Kamal H Masaki, Richard C Allsopp, D Craig Willcox, Ayako Elliott, Bradley J Willcox
FOXO3 has been implicated in longevity in multiple populations. By DNA sequencing in long-lived individuals, we identified all single nucleotide polymorphisms (SNPs) in FOXO3 and showed 41 were associated with longevity. Thirteen of these had predicted alterations in transcription factor binding sites. Those SNPs appeared to be in physical contact, via RNA polymerase II binding chromatin looping, with sites in the FOXO3 promoter, and likely function together as a cis-regulatory unit. The SNPs exhibited a high degree of LD in the Asian population, in which they define a specific longevity haplotype that is relatively common...
July 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28712921/selective-regulation-of-biological-processes-by-vitamin-d-based-on-the-spatio-temporal-cistrome-of-its-receptor
#11
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 24h ligand stimulation comprising >11,600 genomic loci, 78% of which were detected exclusively after 24h. In contrast, a group of 510 persistent VDR sites occurred at all conditions and some 2100 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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
August 2017: Nature Genetics
https://www.readbyqxmd.com/read/28662178/genetic-association-of-fto-irx-region-with-obesity-and-overweight-in-the-polish-population
#18
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
#19
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
#20
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...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
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