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https://www.readbyqxmd.com/read/28070687/predicting-chromatin-architecture-from-models-of-polymer-physics
#1
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/28064247/genome-wide-analysis-of-the-distinct-types-of-chromatin-interactions-in-arabidopsis-thaliana
#2
Jingjing Wang, Yincong Zhou, Xue Li, Xianwen Meng, Miao Fan, Hongjun Chen, Jitong Xue, Ming Chen
The three-dimensional shapes of chromosomes regulate gene expression and genome function. Our knowledge of the role of chromatin interaction is evolving rapidly. Here, we present a study of global chromatin interaction patterns in Arabidopsis thaliana. High-throughput experimental techniques have been developed to map long-range interactions within chromatin. We have integrated data from multiple experimental sources including Hi-C, BS-seq, ChIP-chip and ChIP-seq data for 17 epigenetic marks and 35 transcription factors...
November 15, 2016: Plant & Cell Physiology
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
#3
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
#4
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/28035029/geneattribution-trait-agnostic-identification-of-candidate-genes-associated-with-noncoding-variation
#5
Arthur Wuster, Diana Chang, Timothy W Behrens, Tushar R Bhangale
MOTIVATION: We have developed geneAttribution, an R package that assigns candidate causal gene(s) to a risk variant identified by a genetic association study such as a GWAS. The method combines user-supplied functional annotation such as expression quantitative trait loci (eQTL) or Hi-C genome conformation data and reports the most likely candidate genes. In the absence of annotation data, geneAttribution relies on the distances between the genes and the input variant. AVAILABILITY AND IMPLEMENTATION: The package is freely available from http://www...
December 28, 2016: Bioinformatics
https://www.readbyqxmd.com/read/28027298/inferential-structure-determination-of-chromosomes-from-single-cell-hi-c-data
#6
Simeon Carstens, Michael Nilges, Michael Habeck
Chromosome conformation capture (3C) techniques have revealed many fascinating insights into the spatial organization of genomes. 3C methods typically provide information about chromosomal contacts in a large population of cells, which makes it difficult to draw conclusions about the three-dimensional organization of genomes in individual cells. Recently it became possible to study single cells with Hi-C, a genome-wide 3C variant, demonstrating a high cell-to-cell variability of genome organization. In principle, restraint-based modeling should allow us to infer the 3D structure of chromosomes from single-cell contact data, but suffers from the sparsity and low resolution of chromosomal contacts...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27976707/a-pathway-centric-view-of-spatial-proximity-in-the-3d-nucleome-across-cell-lines
#7
Hiren Karathia, Carl Kingsford, Michelle Girvan, Sridhar Hannenhalli
In various contexts, spatially proximal genes have been shown to be functionally related. However, the extent to which spatial proximity of genes in a pathway contributes to the pathway's context-specific activity is not known. Leveraging Hi-C data in six human cell-lines, we show that spatial proximity of genes in a pathway is highly correlated with the pathway's context-specific expression and function. Furthermore, spatial proximity of pathway genes correlates with interactions of their protein products, and the specific pathway genes that are proximal to one another tend to occupy higher levels in the regulatory hierarchy...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27940952/hapcut2-robust-and-accurate-haplotype-assembly-for-diverse-sequencing-technologies
#8
Peter Edge, Vineet Bafna, Vikas Bansal
Many tools have been developed for haplotype assembly - the reconstruction of individual haplotypes using reads mapped to a reference genome sequence. Due to increasing interest in obtaining haplotype-resolved human genomes, a range of new sequencing protocols and technologies have been developed to enable the reconstruction of whole-genome haplotypes. However, existing computational methods designed to handle specific technologies do not scale well on data from different protocols. We describe a new algorithm, HapCUT2, that extends our previous method (HapCUT) to handle multiple sequencing technologies...
December 9, 2016: Genome Research
https://www.readbyqxmd.com/read/27899641/3d-genome-structure-modeling-by-lorentzian-objective-function
#9
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
#10
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
#11
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...
December 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27863249/lineage-specific-genome-architecture-links-enhancers-and-non-coding-disease-variants-to-target-gene-promoters
#12
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
#13
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
#14
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...
December 27, 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
#15
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
#16
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
#17
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
#18
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
#19
Shoukai Yu, Bernardo Lemos
Ribosomal RNAs (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, whereas 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)...
December 31, 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
#20
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...
December 2016: Genome Research
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