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https://www.readbyqxmd.com/read/28623585/in-situ-hi-c-library-preparation-for-plants-to-study-their-three-dimensional-chromatin-interactions-on-a-genome-wide-scale
#1
Chang Liu
The spatial organization of the genome in the nucleus is critical for many cellular processes. It has been broadly accepted that the packing of chromatin inside the nucleus is not random, but structured at several hierarchical levels. The Hi-C method combines Chromatin Conformation Capture and high-throughput sequencing, which allows interrogating genome-wide chromatin interactions. Depending on the sequencing depth, chromatin packing patterns derived from Hi-C experiments can be viewed on a chromosomal scale or at a local genic level...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28604728/identification-of-19-new-risk-loci-and-potential-regulatory-mechanisms-influencing-susceptibility-to-testicular-germ-cell-tumor
#2
Kevin Litchfield, Max Levy, Giulia Orlando, Chey Loveday, Philip J Law, Gabriele Migliorini, Amy Holroyd, Peter Broderick, Robert Karlsson, Trine B Haugen, Wenche Kristiansen, Jérémie Nsengimana, Kerry Fenwick, Ioannis Assiotis, ZSofia Kote-Jarai, Alison M Dunning, Kenneth Muir, Julian Peto, Rosalind Eeles, Douglas F Easton, Darshna Dudakia, Nick Orr, Nora Pashayan, D Timothy Bishop, Alison Reid, Robert A Huddart, Janet Shipley, Tom Grotmol, Fredrik Wiklund, Richard S Houlston, Clare Turnbull
Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes...
June 12, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28604723/fish-ing-for-captured-contacts-towards-reconciling-fish-and-3c
#3
Geoffrey Fudenberg, Maxim Imakaev
Chromosome conformation capture (3C) and fluorescence in situ hybridization (FISH) are two widely used technologies that provide distinct readouts of 3D chromosome organization. While both technologies can assay locus-specific organization, how to integrate views from 3C, or genome-wide Hi-C, and FISH is far from solved. Contact frequency, measured by Hi-C, and spatial distance, measured by FISH, are often assumed to quantify the same phenomena and used interchangeably. Here, however, we demonstrate that contact frequency is distinct from average spatial distance, both in polymer simulations and in experimental data...
June 12, 2017: Nature Methods
https://www.readbyqxmd.com/read/28604721/comparison-of-computational-methods-for-hi-c-data-analysis
#4
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...
June 12, 2017: Nature Methods
https://www.readbyqxmd.com/read/28588240/structural-modeling-of-chromatin-integrates-genome-features-and-reveals-chromosome-folding-principle
#5
Wen Jun Xie, Luming Meng, Sirui Liu, Ling Zhang, Xiaoxia Cai, Yi Qin Gao
How chromosomes fold into 3D structures and how genome functions are affected or even controlled by their spatial organization remain challenging questions. Hi-C experiment has provided important structural insights for chromosome, and Hi-C data are used here to construct the 3D chromatin structure which are characterized by two spatially segregated chromatin compartments A and B. By mapping a plethora of genome features onto the constructed 3D chromatin model, we show vividly the close connection between genome properties and the spatial organization of chromatin...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28583068/lncrna-screen-an-interactive-platform-for-computationally-screening-long-non-coding-rnas-in-large-genomics-datasets
#6
Yixiao Gong, Hsuan-Ting Huang, Yu Liang, Thomas Trimarchi, Iannis Aifantis, Aristotelis Tsirigos
BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as a class of factors that are important for regulating development and cancer. Computational prediction of lncRNAs from ultra-deep RNA sequencing has been successful in identifying candidate lncRNAs. However, the complexity of handling and integrating different types of genomics data poses significant challenges to experimental laboratories that lack extensive genomics expertise. RESULT: To address this issue, we have developed lncRNA-screen, a comprehensive pipeline for computationally screening putative lncRNA transcripts over large multimodal datasets...
June 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28582503/hugin-hi-c-unifying-genomic-interrogator
#7
Joshua S Martin, Zheng Xu, Alex P Reiner, Karen L Mohlke, Patrick Sullivan, Bing Ren, Ming Hu, Yun Li
Motivation: High throughput chromatin conformation capture (3C) technologies, such as Hi-C and ChIA-PET, have the potential to elucidate the functional roles of non-coding variants. However, most of published genome-wide unbiased chromatin organization studies have used cultured cell lines, limiting their generalizability. Results: We developed a web browser, HUGIn, to visualize Hi-C data generated from 21 human primary tissues and cell lines. HUGIn enables assessment of chromatin contacts both constitutive across and specific to tissue(s) and/or cell line(s) at any genomic loci, including GWAS SNPs, eQTLs and cis-regulatory elements, facilitating the understanding of both GWAS and eQTLs results and functional genomics data...
June 5, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28575119/nucleolus-association-of-chromosomal-domains-is-largely-maintained-in-cellular-senescence-despite-massive-nuclear-reorganisation
#8
Stefan Dillinger, Tobias Straub, Attila Németh
Mammalian chromosomes are organized in structural and functional domains of 0.1-10 Mb, which are characterized by high self-association frequencies in the nuclear space and different contact probabilities with nuclear sub-compartments. They exhibit distinct chromatin modification patterns, gene expression levels and replication timing. Recently, nucleolus-associated chromosomal domains (NADs) have been discovered, yet their precise genomic organization and dynamics are still largely unknown. Here, we use nucleolus genomics and single-cell experiments to address these questions in human embryonic fibroblasts during replicative senescence...
2017: PloS One
https://www.readbyqxmd.com/read/28573677/physical-properties-of-the-chromosomes-and-implications-for-development
#9
REVIEW
Takeshi Sugawara, Akatsuki Kimura
Remarkable progress has been made in understanding chromosome structures inside the cell nucleus. Recent advances in Hi-C technologies enable the detection of genome-wide chromatin interactions, providing insight into three-dimensional (3D) genome organization. Advancements in the spatial and temporal resolutions of imaging as well as in molecular biological techniques allow the tracking of specific chromosomal loci, improving our understanding of chromosome movements. From these data, we are beginning to understand how the intra-nuclear locations of chromatin loci and the 3D genome structure change during development and differentiation...
June 2, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28544514/dynamic-enhancer-function-in-the-chromatin-context
#10
REVIEW
Ido Goldstein, Gordon L Hager
Enhancers serve as critical regulatory elements in higher eukaryotic cells. The characterization of enhancer function has evolved primarily from genome-wide methodologies, including chromatin immunoprecipitation (ChIP-seq), DNase-I hypersensitivity (DNase-seq), digital genomic footprinting (DGF), and the chromosome conformation capture techniques (3C, 4C, and Hi-C). These population-based assays average signals across millions of cells and lead to enhancer models characterized by static and sequential binding...
May 22, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28513628/an-integrated-model-for-detecting-significant-chromatin-interactions-from-high-resolution-hi-c-data
#11
Mark Carty, Lee Zamparo, Merve Sahin, Alvaro González, Raphael Pelossof, Olivier Elemento, Christina S Leslie
Here we present HiC-DC, a principled method to estimate the statistical significance (P values) of chromatin interactions from Hi-C experiments. HiC-DC uses hurdle negative binomial regression account for systematic sources of variation in Hi-C read counts-for example, distance-dependent random polymer ligation and GC content and mappability bias-and model zero inflation and overdispersion. Applied to high-resolution Hi-C data in a lymphoblastoid cell line, HiC-DC detects significant interactions at the sub-topologically associating domain level, identifying potential structural and regulatory interactions supported by CTCF binding sites, DNase accessibility, and/or active histone marks...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28510289/genome-organization-during-the-cell-cycle-unity-in-division
#12
REVIEW
Rosela Golloshi, Jacob T Sanders, Rachel Patton McCord
During the cell cycle, the genome must undergo dramatic changes in structure, from a decondensed, yet highly organized interphase structure to a condensed, generic mitotic chromosome and then back again. For faithful cell division, the genome must be replicated and chromosomes and sister chromatids physically segregated from one another. Throughout these processes, there is feedback and tension between the information-storing role and the physical properties of chromosomes. With a combination of recent techniques in fluorescence microscopy, chromosome conformation capture (Hi-C), biophysical experiments, and computational modeling, we can now attribute mechanisms to many long-observed features of chromosome structure changes during cell division...
May 16, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28496157/rna-seq-based-genome-wide-analysis-reveals-loss-of-inter-chromosomal-regulation-in-breast-cancer
#13
Jesús Espinal-Enríquez, Cristóbal Fresno, Guillermo Anda-Jáuregui, Enrique Hernández-Lemus
Breast cancer is a complex heterogeneous disease. Common hallmark features of cancer can be found. Their origin may be traced back to their intricate relationships governing regulatory programs during the development of this disease. To unveil distinctive features of the transcriptional regulation program in breast cancer, a pipeline for RNA-seq analysis in 780 breast cancer and 101 healthy breast samples, at gene expression and network level, was implemented. Inter-chromosomal relationships between genes resulted strikingly scarce in a cancer network, in comparison to its healthy counterpart...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490498/shelterin-components-mediate-genome-reorganization-in-response-to-replication-stress
#14
Takeshi Mizuguchi, Nitika Taneja, Emiko Matsuda, Jon-Matthew Belton, Peter FitzGerald, Job Dekker, Shiv I S Grewal
The dynamic nature of genome organization impacts critical nuclear functions including the regulation of gene expression, replication, and DNA damage repair. Despite significant progress, the mechanisms responsible for reorganization of the genome in response to cellular stress, such as aberrant DNA replication, are poorly understood. Here, we show that fission yeast cells carrying a mutation in the DNA-binding protein Sap1 show defects in DNA replication progression and genome stability and display extensive changes in genome organization...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28475875/dynamic-rewiring-of-promoter-anchored-chromatin-loops-during-adipocyte-differentiation
#15
Rasmus Siersbæk, Jesper Grud Skat Madsen, Biola Maria Javierre, Ronni Nielsen, Emilie Kristine Bagge, Jonathan Cairns, Steven William Wingett, Sofie Traynor, Mikhail Spivakov, Peter Fraser, Susanne Mandrup
Interactions between transcriptional promoters and their distal regulatory elements play an important role in transcriptional regulation; however, the extent to which these interactions are subject to rapid modulations in response to signals is unknown. Here, we use promoter capture Hi-C to demonstrate a rapid reorganization of promoter-anchored chromatin loops within 4 hr after inducing differentiation of 3T3-L1 preadipocytes. The establishment of new promoter-enhancer loops is tightly coupled to activation of poised (histone H3 lysine 4 mono- and dimethylated) enhancers, as evidenced by the acquisition of histone H3 lysine 27 acetylation and the binding of MED1, SMC1, and P300 proteins to these regions, as well as to activation of target genes...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28475589/long-range-control-of-gene-expression-via-rna-directed-dna-methylation
#16
M Jordan Rowley, M Hafiz Rothi, Gudrun Böhmdorfer, Jan Kuciński, Andrzej T Wierzbicki
RNA-mediated transcriptional silencing, in plants known as RNA-directed DNA methylation (RdDM), is a conserved process where small interfering RNA (siRNA) and long non-coding RNA (lncRNA) help establish repressive chromatin modifications. This process represses transposons and affects the expression of protein-coding genes. We found that in Arabidopsis thaliana AGO4 binding sites are often located distant from genes differentially expressed in ago4. Using Hi-C to compare interactions between genotypes, we show that RdDM-targeted loci have the potential to engage in chromosomal interactions, but these interactions are inhibited in wild-type conditions...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28472433/exploring-spatially-adjacent-tfbs-clustered-regions-with-hi-c-data
#17
Hebing Chen, Shuai Jiang, Zhuo Zhang, Hao Li, Yiming Lu, Xiaochen Bo
Motivation: Transcription factor binding sites (TFBSs) are clustered in the human genome, forming the TFBS-clustered regions that regulate gene transcription, which requires dynamic chromatin configurations between promoters and distal regulatory elements. Here, we propose a regulatory model called spatially adjacent TFBS-clustered regions (SAT), in which TFBS-clustered regions are connected by spatial proximity as identified by high-resolution Hi-C data. Results: TFBS-clustered regions forming SATs appeared less frequently in gene promoters than did isolated TFBS-clustered regions, whereas SATs as a whole appeared more frequently...
May 4, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28468906/whole-genome-restriction-mapping-by-subhaploid-based-rad-sequencing-an-efficient-and-flexible-approach-for-physical-mapping-and-genome-scaffolding
#18
Jinzhuang Dou, Huaiqian Dou, Chuang Mu, Lingling Zhang, Yangping Li, Jia Wang, Tianqi Li, Yuli Li, Xiaoli Hu, Shi Wang, Zhenmin Bao
Assembly of complex genomes using short reads remains a major challenge, which usually yields highly fragmented assemblies. Generation of ultra-dense linkage maps is promising for anchoring such assemblies, but traditional linkage mapping methods are hindered by the infrequency and unevenness of meiotic recombination that limit attainable map resolution. Here we develop a sequencing-based "in vitro" linkage mapping approach (called RadMap), where chromosome breakage and segregation are realized by generating hundreds of "subhaploid" fosmid/BAC clone pools, and by restriction site-associated DNA (RAD) sequencing of these clone pools to produce an ultra-dense whole-genome restriction map to facilitate genome scaffolding...
May 3, 2017: Genetics
https://www.readbyqxmd.com/read/28468672/inferring-the-physical-properties-of-yeast-chromatin-through-bayesian-analysis-of-whole-nucleus-simulations
#19
Jean-Michel Arbona, Sébastien Herbert, Emmanuelle Fabre, Christophe Zimmer
BACKGROUND: The structure and mechanical properties of chromatin impact DNA functions and nuclear architecture but remain poorly understood. In budding yeast, a simple polymer model with minimal sequence-specific constraints and a small number of structural parameters can explain diverse experimental data on nuclear architecture. However, how assumed chromatin properties affect model predictions was not previously systematically investigated. RESULTS: We used hundreds of dynamic chromosome simulations and Bayesian inference to determine chromatin properties consistent with an extensive dataset that includes hundreds of measurements from imaging in fixed and live cells and two Hi-C studies...
May 3, 2017: Genome Biology
https://www.readbyqxmd.com/read/28467502/correction-gothic-a-probabilistic-model-to-resolve-complex-biases-and-to-identify-real-interactions-in-hi-c-data
#20
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0174744.].
2017: PloS One
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