scholarly journals Specific Virus-Host Genome Interactions Revealed by Tethered Chromosome Conformation Capture

2017 ◽  
Author(s):  
Haochen Li ◽  
Reza Kalhor ◽  
Bing Li ◽  
Trent Su ◽  
Arnold J. Berk ◽  
...  
Keyword(s):  
Genome Structure ◽  
Three Dimensional ◽  
Chromosome Conformation Capture ◽  
Host Genome ◽  
Host Cells ◽  
Chromosome Conformation ◽  
Human Lung Fibroblast ◽  
A Genome ◽  
Specific Virus ◽  
Genome Interactions

AbstractViruses have evolved a variety of mechanisms to interact with host cells for their adaptive benefits, including subverting host immune responses and hijacking host DNA replication/transcription machineries [1–3]. Although interactions between viral and host proteins have been studied extensively, little is known about how the vial genome may interact with the host genome and how such interactions could affect the activities of both the virus and the host cell. Since the three-dimensional organization of a genome can have significant impact on genomic activities such as transcription and replication, we hypothesize that such structure-based regulation of genomic functions also applies to viral genomes depending on their association with host genomic regions and their spatial locations inside the nucleus. Here, we used Tethered Chromosome Conformation Capture (TCC) to investigate viral-host genome interactions between the adenovirus and human lung fibroblast cells. We found viral-host genome interactions were enriched in certain active chromatin regions and chromatin domains marked by H3K27me3. The contacts by viral DNA seems to impact the structure and function of the host genome, leading to remodeling of the fibroblast epigenome. Our study represents the first comprehensive analysis of viral-host interactions at the genome structure level, revealing unexpectedly specific virus-host genome interactions. The non-random nature of such interactions indicates a deliberate but poorly understood mechanism for targeting of host DNA by foreign genomes.

scholarly journals GSDB: a database of 3D chromosome and genome structures reconstructed from Hi-C data

2019 ◽  
Author(s):  
Oluwatosin Oluwadare ◽  
Max Highsmith ◽  
Jianlin Cheng
Keyword(s):  
Structure Prediction ◽  
Biological Activities ◽  
Genome Structure ◽  
3D Structure ◽  
Three Dimensional ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Reconstruction Methods ◽  
A Genome ◽  
Structure Reconstruction

ABSTRACTAdvances in the study of chromosome conformation capture (3C) technologies, such as Hi-C technique - capable of capturing chromosomal interactions in a genome-wide scale - have led to the development of three-dimensional (3D) chromosome and genome structure reconstruction methods from Hi-C data. The 3D genome structure is important because it plays a role in a variety of important biological activities such as DNA replication, gene regulation, genome interaction, and gene expression. In recent years, numerous Hi-C datasets have been generated, and likewise, a number of genome structure construction algorithms have been developed. However, until now, there has been no freely available repository for 3D chromosome structures. In this work, we outline the construction of a novel Genome Structure Database (GSDB) to create a comprehensive repository that contains 3D structures for Hi-C datasets constructed by a variety of 3D structure reconstruction tools. GSDB contains over 50,000 structures constructed by 12 state-of-the-art chromosome and genome structure prediction methods for publicly used Hi-C datasets with varying resolution. The database is useful for the community to study the function of genome from a 3D perspective. GSDB is accessible at http://sysbio.rnet.missouri.edu/3dgenome/GSDB

scholarly journals The DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 289 ◽  
Author(s):  
Ping Hong ◽  
Hao Jiang ◽  
Weize Xu ◽  
Da Lin ◽  
Qian Xu ◽  
...  
Keyword(s):  
Target Genes ◽  
High Efficiency ◽  
New Technology ◽  
Three Dimensional ◽  
Large Data ◽  
Regulatory Elements ◽  
Chromosome Conformation Capture ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
3D Genome

It is becoming increasingly important to understand the mechanism of regulatory elements on target genes in long-range genomic distance. 3C (chromosome conformation capture) and its derived methods are now widely applied to investigate three-dimensional (3D) genome organizations and gene regulation. Digestion-ligation-only Hi-C (DLO Hi-C) is a new technology with high efficiency and cost-effectiveness for whole-genome chromosome conformation capture. Here, we introduce the DLO Hi-C tool, a flexible and versatile pipeline for processing DLO Hi-C data from raw sequencing reads to normalized contact maps and for providing quality controls for different steps. It includes more efficient iterative mapping and linker filtering. We applied the DLO Hi-C tool to different DLO Hi-C datasets and demonstrated its ability in processing large data with multithreading. The DLO Hi-C tool is suitable for processing DLO Hi-C and in situ DLO Hi-C datasets. It is convenient and efficient for DLO Hi-C data processing.

scholarly journals The three-dimensional genome organization of Drosophila melanogaster through data integration

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Qingjiao Li ◽  
Harianto Tjong ◽  
Xiao Li ◽  
Ke Gong ◽  
Xianghong Jasmine Zhou ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Data Integration ◽  
Genome Organization ◽  
Genome Structure ◽  
Three Dimensional ◽  
Structural Features ◽  
Embryonic Cells ◽  
Data Types ◽  
Chromosome Conformation ◽  
Topological Domains

Abstract Background Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize the accuracy and coverage of three-dimensional genome structural models, it is important to integrate all available sources of experimental information about a genome’s organization. It remains a major challenge to integrate such data from various complementary experimental methods. Here, we present an approach for data integration to determine a population of complete three-dimensional genome structures that are statistically consistent with data from both genome-wide chromosome conformation capture (Hi-C) and lamina-DamID experiments. Results Our structures resolve the genome at the resolution of topological domains, and reproduce simultaneously both sets of experimental data. Importantly, this data deconvolution framework allows for structural heterogeneity between cells, and hence accounts for the expected plasticity of genome structures. As a case study we choose Drosophila melanogaster embryonic cells, for which both data types are available. Our three-dimensional genome structures have strong predictive power for structural features not directly visible in the initial data sets, and reproduce experimental hallmarks of the D. melanogaster genome organization from independent and our own imaging experiments. Also they reveal a number of new insights about genome organization and its functional relevance, including the preferred locations of heterochromatic satellites of different chromosomes, and observations about homologous pairing that cannot be directly observed in the original Hi-C or lamina-DamID data. Conclusions Our approach allows systematic integration of Hi-C and lamina-DamID data for complete three-dimensional genome structure calculation, while also explicitly considering genome structural variability.

scholarly journals Structural features of the fly chromatin colors revealed by automatic three-dimensional modeling.

2016 ◽  
Author(s):  
François Serra ◽  
Davide Baù ◽  
Guillaume Filion ◽  
Marc A. Marti-Renom
Keyword(s):  
Spatial Organization ◽  
Three Dimensional ◽  
Structural Features ◽  
Three Dimensions ◽  
Chromosome Conformation ◽  
Three Dimensional Modeling ◽  
Genomic Technologies ◽  
A Genome ◽  
Contact Data ◽  
Three Dimensional Models

The sequence of a genome is insufficient to understand all genomic processes carried out in the cell nucleus. To achieve this, the knowledge of its three- dimensional architecture is necessary. Advances in genomic technologies and the development of new analytical methods, such as Chromosome Conformation Capture (3C) and its derivatives, now permit to investigate the spatial organization of genomes. However, inferring structures from raw contact data is a tedious process for shortage of available tools. Here we present TADbit, a computational framework to analyze and model the chromatin fiber in three dimensions. To illustrate the use of TADbit, we automatically modeled 50 genomic domains from the fly genome revealing differential structural features of the previously defined chromatin colors, establishing a link between the conformation of the genome and the local chromatin composition. More generally, TADbit allows to obtain three-dimensional models ready for visualization from 3C-based experiments and to characterize their relation to gene expression and epigenetic states. TADbit is open-source and available for download from http://www.3DGenomes.org.

scholarly journals RUNX1-mediated alphaherpesvirus-host trans-species chromatin interaction promotes viral transcription

2021 ◽  
Vol 7 (26) ◽  
pp. eabf8962
Author(s):  
Ke Xiao ◽  
Dan Xiong ◽  
Gong Chen ◽  
Jinsong Yu ◽  
Yue Li ◽  
...  
Keyword(s):  
Pseudorabies Virus ◽  
Host Cells ◽  
Chromatin Interaction ◽  
Open Chromatin ◽  
Chromosome Conformation ◽  
Dna Viruses ◽  
Genome Wide ◽  
A Genome ◽  
Genome Transcription ◽  
Active Transcription

Like most DNA viruses, herpesviruses precisely deliver their genomes into the sophisticatedly organized nuclei of the infected host cells to initiate subsequent transcription and replication. However, it remains elusive how the viral genome specifically interacts with the host genome and hijacks host transcription machinery. Using pseudorabies virus (PRV) as model virus, we performed chromosome conformation capture assays to demonstrate a genome-wide specific trans-species chromatin interaction between the virus and host. Our data show that the PRV genome is delivered by the host DNA binding protein RUNX1 into the open chromatin and active transcription zone. This facilitates virus hijacking host RNAPII to efficiently transcribe viral genes, which is significantly inhibited by either a RUNX1 inhibitor or RNA interference. Together, these findings provide insights into the chromatin interaction between viral and host genomes and identify new areas of research to advance the understanding of herpesvirus genome transcription.

scholarly journals GenomeDISCO: A concordance score for chromosome conformation capture experiments using random walks on contact map graphs

2017 ◽  
Author(s):  
Oana Ursu ◽  
Nathan Boley ◽  
Maryna Taranova ◽  
Y.X. Rachel Wang ◽  
Galip Gurkan Yardimci ◽  
...  
Keyword(s):  
Random Walks ◽  
Critical Role ◽  
Three Dimensional ◽  
Cell Types ◽  
Chromosome Conformation Capture ◽  
Supplementary Information ◽  
Contact Map ◽  
Chromosome Conformation ◽  
Contact Maps ◽  
Map Graphs

AbstractMotivationThe three-dimensional organization of chromatin plays a critical role in gene regulation and disease. High-throughput chromosome conformation capture experiments such as Hi-C are used to obtain genome-wide maps of 3D chromatin contacts. However, robust estimation of data quality and systematic comparison of these contact maps is challenging due to the multi-scale, hierarchical structure of chromatin contacts and the resulting properties of experimental noise in the data. Measuring concordance of contact maps is important for assessing reproducibility of replicate experiments and for modeling variation between different cellular contexts.ResultsWe introduce a concordance measure called GenomeDISCO (DIfferences between Smoothed COntact maps) for assessing the similarity of a pair of contact maps obtained from chromosome conformation capture experiments. The key idea is to smooth contact maps using random walks on the contact map graph, before estimating concordance. We use simulated datasets to benchmark GenomeDISCO’s sensitivity to different types of noise that affect chromatin contact maps. When applied to a large collection of Hi-C datasets, GenomeDISCO accurately distinguishes biological replicates from samples obtained from different cell types. GenomeDISCO also generalizes to other chromosome conformation capture assays, such as HiChIP.AvailabilitySoftware implementing GenomeDISCO is available at https://github.com/kundajelab/[email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals A combination of transcription factors mediates inducible interchromosomal pairing

2018 ◽  
Author(s):  
Seungsoo Kim ◽  
Maitreya J Dunham ◽  
Jay Shendure
Keyword(s):  
Transcription Factors ◽  
Binding Site ◽  
Molecular Mechanism ◽  
Dna Sequences ◽  
Three Dimensional ◽  
Chromosome Conformation ◽  
Homolog Pairing ◽  
A Genome ◽  
Repressor Complex ◽  
Necessary And Sufficient

SummaryRemodeling of the three-dimensional organization of a genome has been previously described (e.g. condition-specific pairing or looping), but it remains unknown which factors specify and mediate such shifts in chromosome conformation. Here we describe an assay, MAP-C (Mutation Analysis in Pools by Chromosome conformation capture), that enables the simultaneous characterization of hundreds of cis or trans-acting mutations for their effects on a chromosomal contact or loop. As a proof of concept, we applied MAP-C to systematically dissect the molecular mechanism of inducible interchromosomal pairing between HAS1pr-TDA1pr alleles in Saccharomyces yeast. We identified three transcription factors, Leu3, Sdd4 (Ypr022c), and Rgt1, whose collective binding to nearby DNA sequences is necessary and sufficient for inducible pairing between binding site clusters. Rgt1 contributes to the regulation of pairing, both through changes in expression level and through its interactions with the Tup1/Ssn6 repressor complex. HAS1pr-TDA1pr is the only locus with a cluster of binding site motifs for all three factors in both S. cerevisiae and S. uvarum genomes, but the promoter for HXT3, which contains Leu3 and Rgt1 motifs, also exhibits inducible homolog pairing. Altogether, our results demonstrate that specific combinations of transcription factors can mediate condition-specific interchromosomal contacts, and reveal a molecular mechanism for interchromosomal contacts and mitotic homolog pairing.

scholarly journals Three-Dimensional Genome Interactions Identify Potential Adipocyte Metabolism-Associated Gene STON1 and Immune-Correlated Gene FSHR at the rs13405728 Locus in Polycystic Ovary Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Can-hui Cao ◽  
Ye Wei ◽  
Rang Liu ◽  
Xin-ran Lin ◽  
Jia-qi Luo ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Target Genes ◽  
Polycystic Ovary ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Ovary Syndrome ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Caucasian Women ◽  
Genome Interactions

Backgroundrs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined.MethodsThree-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns.ResultsGenerally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 (P=0.0423) and FSHR (P=0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes (P=0.0008) in adipocytes (P=0.0001), which was validated in the fat tissue (P<0.0001) and ovary (P=0.0035) from fat-diet mice. The immune system process (GO:0002376) was enriched in FSHR co-expressed genes (P=0.0002) and PCOS patients (P=0.0002), with CD4 high expression in PCOS patients (P=0.0316) and PCOS-like models (P=0.0079). Meanwhile, FSHR expression was positively correlated with CD4 expression in PCOS patients (P=0.0252) and PCOS-like models (P=0.0178). Furthermore, androgen receptor (AR) was identified as the common transcription factor for STON1 and FSHR and positively correlated with the expression of STON1 (P=0.039) and FSHR (P=4e-06) in ovary tissues and PCOS-like mice.ConclusionOverall, we identified STON1 and FSHR as potential targets for the rs13405728 locus and their roles in the processes of adipocyte metabolism and CD4 immune expression in PCOS, which provides 3D genomic insight into the pathogenesis of PCOS.

scholarly journals Three-dimensional chromatin in infectious disease—A role for gene regulation and pathogenicity?

2021 ◽  
Vol 17 (2) ◽  
pp. e1009207
Author(s):  
Sage Z. Davis ◽  
Thomas Hollin ◽  
Todd Lenz ◽  
Karine G. Le Roch
Keyword(s):  
Infectious Disease ◽  
Gene Regulation ◽  
High Throughput Sequencing ◽  
Three Dimensional ◽  
Nuclear Architecture ◽  
Host Cells ◽  
Chromosome Conformation ◽  
Infectious Disease Research ◽  
Genome Wide

The recent Coronavirus Disease 2019 pandemic has once again reminded us the importance of understanding infectious diseases. One important but understudied area in infectious disease research is the role of nuclear architecture or the physical arrangement of the genome in the nucleus in controlling gene regulation and pathogenicity. Recent advances in research methods, such as Genome-wide chromosome conformation capture using high-throughput sequencing (Hi-C), have allowed for easier analysis of nuclear architecture and chromosomal reorganization in both the infectious disease agents themselves as well as in their host cells. This review will discuss broadly on what is known about nuclear architecture in infectious disease, with an emphasis on chromosomal reorganization, and briefly discuss what steps are required next in the field.

A statistical model of intra-chromosome contact maps

Soft Matter ◽  
2015 ◽  
Vol 11 (5) ◽  
pp. 1019-1025 ◽  
Author(s):  
Leonid I. Nazarov ◽  
Mikhail V. Tamm ◽  
Vladik A. Avetisov ◽  
Sergei K. Nechaev
Keyword(s):  
Fine Structure ◽  
Statistical Model ◽  
Chromosome Conformation Capture ◽  
Chromosome Conformation ◽  
Contact Maps ◽  
Genome Wide ◽  
A Genome ◽  
Capture Method ◽  
Chromosome Maps

A statistical model describing a fine structure of the intra-chromosome maps obtained by a genome-wide chromosome conformation capture method (Hi–C) is proposed.

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