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https://www.readbyqxmd.com/read/27899641/3d-genome-structure-modeling-by-lorentzian-objective-function
#1
Tuan Trieu, Jianlin Cheng
The 3D structure of the genome plays a vital role in biological processes such as gene interaction, gene regulation, DNA replication and genome methylation. Advanced chromosomal conformation capture techniques, such as Hi-C and tethered conformation capture, can generate chromosomal contact data that can be used to computationally reconstruct 3D structures of the genome. We developed a novel restraint-based method that is capable of reconstructing 3D genome structures utilizing both intra-and inter-chromosomal contact data...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899590/different%C3%A2-enhancer-classes-in-drosophila-bind-distinct-architectural-proteins-and-mediate-unique-chromatin-interactions-and-3d-architecture
#2
Caelin Cubeñas-Potts, M Jordan Rowley, Xiaowen Lyu, Ge Li, Elissa P Lei, Victor G Corces
Eukaryotic gene expression is regulated by enhancer-promoter interactions but the molecular mechanisms that govern specificity have remained elusive. Genome-wide studies utilizing STARR-seq identified two enhancer classes in Drosophila that interact with different core promoters: housekeeping enhancers (hkCP) and developmental enhancers (dCP). We hypothesized that the two enhancer classes are occupied by distinct architectural proteins, affecting their enhancer-promoter contacts. By evaluating ChIP-seq occupancy of architectural proteins, typical enhancer-associated proteins, and histone modifications, we determine that both enhancer classes are enriched for RNA Polymerase II, CBP, and architectural proteins but there are also distinctions...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27867007/srf-co-factors-control-the-balance-between-cell-proliferation-and-contractility
#3
Francesco Gualdrini, Cyril Esnault, Stuart Horswell, Aengus Stewart, Nik Matthews, Richard Treisman
The ERK-regulated ternary complex factors (TCFs) act with the transcription factor serum response factor (SRF) to activate mitogen-induced transcription. However, the extent of their involvement in the immediate-early transcriptional response, and their wider functional significance, has remained unclear. We show that, in MEFs, TCF inactivation significantly inhibits over 60% of TPA-inducible gene transcription and impairs cell proliferation. Using integrated SRF ChIP-seq and Hi-C data, we identified over 700 TCF-dependent SRF direct target genes involved in signaling, transcription, and proliferation...
November 5, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27863249/lineage-specific-genome-architecture-links-enhancers-and-non-coding-disease-variants-to-target-gene-promoters
#4
Biola M Javierre, Oliver S Burren, Steven P Wilder, Roman Kreuzhuber, Steven M Hill, Sven Sewitz, Jonathan Cairns, Steven W Wingett, Csilla Várnai, Michiel J Thiecke, Frances Burden, Samantha Farrow, Antony J Cutler, Karola Rehnström, Kate Downes, Luigi Grassi, Myrto Kostadima, Paula Freire-Pritchett, Fan Wang, Hendrik G Stunnenberg, John A Todd, Daniel R Zerbino, Oliver Stegle, Willem H Ouwehand, Mattia Frontini, Chris Wallace, Mikhail Spivakov, Peter Fraser
Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27861577/identifying-causal-genes-at-the-multiple-sclerosis-associated-region-6q23-using-capture-hi-c
#5
Paul Martin, Amanda McGovern, Jonathan Massey, Stefan Schoenfelder, Kate Duffus, Annie Yarwood, Anne Barton, Jane Worthington, Peter Fraser, Stephen Eyre, Gisela Orozco
BACKGROUND: The chromosomal region 6q23 has been found to be associated with multiple sclerosis (MS) predisposition through genome wide association studies (GWAS). There are four independent single nucleotide polymorphisms (SNPs) associated with MS in this region, which spans around 2.5 Mb. Most GWAS variants associated with complex traits, including these four MS associated SNPs, are non-coding and their function is currently unknown. However, GWAS variants have been found to be enriched in enhancers and there is evidence that they may be involved in transcriptional regulation of their distant target genes through long range chromatin looping...
2016: PloS One
https://www.readbyqxmd.com/read/27856763/normal-chromosome-conformation-depends-on-subtelomeric-facultative-heterochromatin-in-neurospora-crassa
#6
Andrew D Klocko, Tereza Ormsby, Jonathan M Galazka, Neena A Leggett, Miki Uesaka, Shinji Honda, Michael Freitag, Eric U Selker
High-throughput chromosome conformation capture (Hi-C) analyses revealed that the 3D structure of the Neurospora crassa genome is dominated by intra- and interchromosomal links between regions of heterochromatin, especially constitutive heterochromatin. Elimination of trimethylation of lysine 9 on histone H3 (H3K9me3) or its binding partner Heterochromatin Protein 1 (HP1)-both prominent features of constitutive heterochromatin-have little effect on the Hi-C pattern. It remained possible that di- or trimethylation of lysine 27 on histone H3 (H3K27me2/3), which becomes localized in regions of constitutive heterochromatin when H3K9me3 or HP1 are lost, plays a critical role in the 3D structure of the genome...
November 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27845379/systems-level-chromosomal-parameters-represent-a-suprachromosomal-basis-for-the-non-random-chromosomal-arrangement-in-human-interphase-nuclei
#7
Sarosh N Fatakia, Ishita S Mehta, Basuthkar J Rao
Forty-six chromosome territories (CTs) are positioned uniquely in human interphase nuclei, wherein each of their positions can range from the centre of the nucleus to its periphery. A non-empirical basis for their non-random arrangement remains unreported. Here, we derive a suprachromosomal basis of that overall arrangement (which we refer to as a CT constellation), and report a hierarchical nature of the same. Using matrix algebra, we unify intrinsic chromosomal parameters (e.g., chromosomal length, gene density, the number of genes per chromosome), to derive an extrinsic effective gene density matrix, the hierarchy of which is dominated largely by extrinsic mathematical coupling of HSA19, followed by HSA17 (human chromosome 19 and 17, both preferentially interior CTs) with all CTs...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27843713/deconvoluting-simulated-metagenomes-the-performance-of-hard-and-soft-clustering-algorithms-applied-to-metagenomic-chromosome-conformation-capture-3c
#8
Matthew Z DeMaere, Aaron E Darling
BACKGROUND: Chromosome conformation capture, coupled with high throughput DNA sequencing in protocols like Hi-C and 3C-seq, has been proposed as a viable means of generating data to resolve the genomes of microorganisms living in naturally occuring environments. Metagenomic Hi-C and 3C-seq datasets have begun to emerge, but the feasibility of resolving genomes when closely related organisms (strain-level diversity) are present in the sample has not yet been systematically characterised...
2016: PeerJ
https://www.readbyqxmd.com/read/27821047/chromosome3d-reconstructing-three-dimensional-chromosomal-structures-from-hi-c-interaction-frequency-data-using-distance-geometry-simulated-annealing
#9
Badri Adhikari, Tuan Trieu, Jianlin Cheng
BACKGROUND: Reconstructing three-dimensional structures of chromosomes is useful for visualizing their shapes in a cell and interpreting their function. In this work, we reconstruct chromosomal structures from Hi-C data by translating contact counts in Hi-C data into Euclidean distances between chromosomal regions and then satisfying these distances using a structure reconstruction method rigorously tested in the field of protein structure determination. RESULTS: We first evaluate the robustness of the overall reconstruction algorithm on noisy simulated data at various levels of noise by comparing with some of the state-of-the-art reconstruction methods...
November 7, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27799070/capture-hi-c-identifies-a-novel-causal-gene-il20ra-in-the-pan-autoimmune-genetic-susceptibility-region-6q23
#10
Amanda McGovern, Stefan Schoenfelder, Paul Martin, Jonathan Massey, Kate Duffus, Darren Plant, Annie Yarwood, Arthur G Pratt, Amy E Anderson, John D Isaacs, Julie Diboll, Nishanthi Thalayasingam, Caroline Ospelt, Anne Barton, Jane Worthington, Peter Fraser, Stephen Eyre, Gisela Orozco
BACKGROUND: The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potential therapeutic targets. Using novel chromatin interaction detection techniques and allele specific assays in T and B cell lines, we provide compelling evidence that redefines causal genes at the 6q23 locus, one of the most important loci that confers autoimmunity risk...
November 1, 2016: Genome Biology
https://www.readbyqxmd.com/read/27797956/a-portrait-of-ribosomal-dna-contacts-with-hi-c-reveals-5s-and-45s-rdna-anchoring-points-in-the-folded-human-genome
#11
Shoukai Yu, Bernardo Lemos
Ribosomal rRNAs account for >60% of all RNAs in eukaryotic cells and are encoded in the ribosomal DNA (rDNA) arrays. The rRNAs are produced from two sets of loci: the 5S rDNA array resides exclusively on human chromosome 1, while the 45S rDNA array resides on the short arm of five human acrocentric chromosomes. The 45S rDNA gives origin to the nucleolus, the nuclear organelle that is the site of ribosome biogenesis. Intriguingly, 5S and 45S rDNA arrays exhibit correlated copy number variation in lymphoblastoid cells (LCLs)...
October 25, 2016: Genome Biology and Evolution
https://www.readbyqxmd.com/read/27789526/an-integrated-3-dimensional-genome-modeling-engine-for-data-driven-simulation-of-spatial-genome-organization
#12
Przemysław Szałaj, Zhonghui Tang, Paul Michalski, Michal J Pietal, Oscar J Luo, Michał Sadowski, Xingwang Li, Kamen Radew, Yijun Ruan, Dariusz Plewczynski
ChIA-PET is a high-throughput mapping technology that reveals long-range chromatin interactions and provides insights into the basic principles of spatial genome organization and gene regulation mediated by specific protein factors. Recently, we showed that a single ChIA-PET experiment provides information at all genomic scales of interest, from the high-resolution locations of binding sites and enriched chromatin interactions mediated by specific protein factors, to the low resolution of nonenriched interactions that reflect topological neighborhoods of higher-order chromosome folding...
October 27, 2016: Genome Research
https://www.readbyqxmd.com/read/27786255/hi-c-constrained-physical-models-of-human-chromosomes-recover-functionally-related-properties-of-genome-organization
#13
Marco Di Stefano, Jonas Paulsen, Tonje G Lien, Eivind Hovig, Cristian Micheletti
Combining genome-wide structural models with phenomenological data is at the forefront of efforts to understand the organizational principles regulating the human genome. Here, we use chromosome-chromosome contact data as knowledge-based constraints for large-scale three-dimensional models of the human diploid genome. The resulting models remain minimally entangled and acquire several functional features that are observed in vivo and that were never used as input for the model. We find, for instance, that gene-rich, active regions are drawn towards the nuclear center, while gene poor and lamina associated domains are pushed to the periphery...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27770354/chromatin-conformation-capture-based-analysis-of-nuclear-architecture
#14
Stefan Grob, Ueli Grossniklaus
Nuclear organization and higher-order chromosome structure in interphase nuclei are thought to have important effects on fundamental biological processes, including chromosome condensation, replication, and transcription. Until recently, however, nuclear organization could only be analyzed microscopically. The development of chromatin conformation capture (3C)-based techniques now allows a detailed look at chromosomal architecture from the level of individual loci to the entire genome. Here we provide a robust Hi-C protocol, allowing the analysis of nuclear organization in nuclei from different wild-type and mutant plant tissues...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734896/3disease-browser-a-web-server-for-integrating-3d-genome-and-disease-associated-chromosome-rearrangement-data
#15
Ruifeng Li, Yifang Liu, Tingting Li, Cheng Li
Chromosomal rearrangement (CR) events have been implicated in many tumor and non-tumor human diseases. CR events lead to their associated diseases by disrupting gene and protein structures. Also, they can lead to diseases through changes in chromosomal 3D structure and gene expression. In this study, we search for CR-associated diseases potentially caused by chromosomal 3D structure alteration by integrating Hi-C and ChIP-seq data. Our algorithm rediscovers experimentally verified disease-associated CRs (polydactyly diseases) that alter gene expression by disrupting chromosome 3D structure...
October 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27725694/three-dimensional-reconstruction-of-single-cell-chromosome-structure-using-recurrence-plots
#16
Yoshito Hirata, Arisa Oda, Kunihiro Ohta, Kazuyuki Aihara
Single-cell analysis of the three-dimensional (3D) chromosome structure can reveal cell-to-cell variability in genome activities. Here, we propose to apply recurrence plots, a mathematical method of nonlinear time series analysis, to reconstruct the 3D chromosome structure of a single cell based on information of chromosomal contacts from genome-wide chromosome conformation capture (Hi-C) data. This recurrence plot-based reconstruction (RPR) method enables rapid reconstruction of a unique structure in single cells, even from incomplete Hi-C information...
October 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27716489/minute-made-data-analysis-tools-for-rapid-interrogation-of-hi-c-contacts
#17
M Jordan Rowley, Victor G Corces
Juicer and Juicebox, described by Durand et al. (2016a, 2016b), are two new tools for fast and reliable processing of Hi-C data, providing approaches for read processing, multiple normalization schemes, feature annotation, and dynamic browsing of chromatin contacts, thus reducing arduous Hi-C analysis into an easy yet flexible pipeline.
October 6, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27706140/formation-of-new-chromatin-domains-determines-pathogenicity-of-genomic-duplications
#18
Martin Franke, Daniel M Ibrahim, Guillaume Andrey, Wibke Schwarzer, Verena Heinrich, Robert Schöpflin, Katerina Kraft, Rieke Kempfer, Ivana Jerković, Wing-Lee Chan, Malte Spielmann, Bernd Timmermann, Lars Wittler, Ingo Kurth, Paola Cambiaso, Orsetta Zuffardi, Gunnar Houge, Lindsay Lambie, Francesco Brancati, Ana Pombo, Martin Vingron, Francois Spitz, Stefan Mundlos
Chromosome conformation capture methods have identified subchromosomal structures of higher-order chromatin interactions called topologically associated domains (TADs) that are separated from each other by boundary regions. By subdividing the genome into discrete regulatory units, TADs restrict the contacts that enhancers establish with their target genes. However, the mechanisms that underlie partitioning of the genome into TADs remain poorly understood. Here we show by chromosome conformation capture (capture Hi-C and 4C-seq methods) that genomic duplications in patient cells and genetically modified mice can result in the formation of new chromatin domains (neo-TADs) and that this process determines their molecular pathology...
October 5, 2016: Nature
https://www.readbyqxmd.com/read/27704558/bone-shaft-revascularization-after-marrow-ablation-is-dramatically-accelerated-in-bsp-mice-along-with-faster-haematopoietic-recolonization
#19
Wafa Bouleftour, Renata Neves Granito, Arnaud Vanden-Bossche, Odile Sabido, Bernard Roche, Mireille Thomas, Marie Thérèse Linossier, Jane E Aubin, Marie-Hélène Lafage-Proust, Laurence Vico, Luc Malaval
The bone organ integrates the activity of bone tissue, bone marrow and blood vessels and the factors ensuring this coordination remain ill defined. Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the Small Integrin Binding Ligand N-Linked Glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis. In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice. We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP + /+ and BSP-/- mice...
October 5, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27692923/genomic-energy-landscapes
#20
Bin Zhang, Peter G Wolynes
Energy landscape theory, developed in the context of protein folding, provides, to our knowledge, a new perspective on chromosome architecture. We review what has been learned concerning the topology and structure of both the interphase and mitotic chromosomes from effective energy landscapes constructed using Hi-C data. Energy landscape thinking raises new questions about the nonequilibrium dynamics of the chromosome and gene regulation.
September 30, 2016: Biophysical Journal
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