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Jocelyn Choy, Melissa J Fullwood
Genomic DNA is dynamically associated with protein factors and folded to form chromatin fibers. The 3-dimensional (3D) configuration of the chromatin will enable the distal genetic elements to come into close proximity, allowing transcriptional regulation. Noncoding RNA can mediate the 3D structure of chromatin. Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) is a valuable and powerful technique in molecular biology which allows the study of unbiased, genome-wide de novo chromatin interactions with paired-end tags...
2017: Methods in Molecular Biology
Maxwell R Mumbach, Adam J Rubin, Ryan A Flynn, Chao Dai, Paul A Khavari, William J Greenleaf, Howard Y Chang
Genome conformation is central to gene control but challenging to interrogate. Here we present HiChIP, a protein-centric chromatin conformation method. HiChIP improves the yield of conformation-informative reads by over 10-fold and lowers the input requirement over 100-fold relative to that of ChIA-PET. HiChIP of cohesin reveals multiscale genome architecture with greater signal-to-background ratios than those of in situ Hi-C.
September 19, 2016: Nature Methods
Guipeng Li, Yang Chen, Michael P Snyder, Michael Q Zhang
ChIA-PET2 is a versatile and flexible pipeline for analyzing different types of ChIA-PET data from raw sequencing reads to chromatin loops. ChIA-PET2 integrates all steps required for ChIA-PET data analysis, including linker trimming, read alignment, duplicate removal, peak calling and chromatin loop calling. It supports different kinds of ChIA-PET data generated from different ChIA-PET protocols and also provides quality controls for different steps of ChIA-PET analysis. In addition, ChIA-PET2 can use phased genotype data to call allele-specific chromatin interactions...
September 12, 2016: Nucleic Acids Research
Kyoung-Dong Kim, Hideki Tanizawa, Osamu Iwasaki, Ken-Ichi Noma
It is becoming clear that structural-maintenance-of-chromosomes (SMC) complexes such as condensin and cohesin are involved in three-dimensional genome organization, yet their exact roles in functional organization remain unclear. We used chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) to comprehensively identify genome-wide associations mediated by condensin and cohesin in fission yeast. We found that although cohesin and condensin often bind to the same loci, they direct different association networks and generate small and larger chromatin domains, respectively...
October 2016: Nature Genetics
Changyong Zhao, Xiaoman Li, Haiyan Hu
The identification of enhancer-target gene (ETG) pairs is vital for the understanding of gene transcriptional regulation. Experimental approaches such as Hi-C have generated valuable resources of ETG pairs. Several computational methods have also been developed to successfully predict ETG interactions. Despite these progresses, high-throughput experimental approaches are still costly and existing computational approaches are still suboptimal and not easy to apply. Here we developed a motif module based approach called PETModule that predicts ETG pairs...
2016: Scientific Reports
Vera Pancaldi, Enrique Carrillo-de-Santa-Pau, Biola Maria Javierre, David Juan, Peter Fraser, Mikhail Spivakov, Alfonso Valencia, Daniel Rico
BACKGROUND: Network analysis is a powerful way of modeling chromatin interactions. Assortativity is a network property used in social sciences to identify factors affecting how people establish social ties. We propose a new approach, using chromatin assortativity, to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts. RESULTS: We use high-resolution promoter capture Hi-C and Hi-Cap data as well as ChIA-PET data from mouse embryonic stem cells to investigate promoter-centered chromatin interaction networks and calculate the presence of specific epigenomic features in the chromatin fragments constituting the nodes of the network...
2016: Genome Biology
Asa Thibodeau, Eladio J Márquez, Oscar Luo, Yijun Ruan, Francesca Menghi, Dong-Guk Shin, Michael L Stitzel, Paola Vera-Licona, Duygu Ucar
UNLABELLED: Recent studies of the human genome have indicated that regulatory elements (e.g. promoters and enhancers) at distal genomic locations can interact with each other via chromatin folding and affect gene expression levels. Genomic technologies for mapping interactions between DNA regions, e.g., ChIA-PET and HiC, can generate genome-wide maps of interactions between regulatory elements. These interaction datasets are important resources to infer distal gene targets of non-coding regulatory elements and to facilitate prioritization of critical loci for important cellular functions...
June 2016: PLoS Computational Biology
Aaron T L Lun, Malcolm Perry, Elizabeth Ing-Simmons
The study of genomic interactions has been greatly facilitated by techniques such as chromatin conformation capture with high-throughput sequencing (Hi-C). These genome-wide experiments generate large amounts of data that require careful analysis to obtain useful biological conclusions. However, development of the appropriate software tools is hindered by the lack of basic infrastructure to represent and manipulate genomic interaction data. Here, we present the InteractionSet package that provides classes to represent genomic interactions and store their associated experimental data, along with the methods required for low-level manipulation and processing of those classes...
2016: F1000Research
Przemyslaw Szalaj, Paul J Michalski, Przemysław Wróblewski, Zhonghui Tang, Michal Kadlof, Giovanni Mazzocco, Yijun Ruan, Dariusz Plewczynski
Recent advances in high-throughput chromosome conformation capture (3C) technology, such as Hi-C and ChIA-PET, have demonstrated the importance of 3D genome organization in development, cell differentiation and transcriptional regulation. There is now a widespread need for computational tools to generate and analyze 3D structural models from 3C data. Here we introduce our 3D GeNOme Modeling Engine (3D-GNOME), a web service which generates 3D structures from 3C data and provides tools to visually inspect and annotate the resulting structures, in addition to a variety of statistical plots and heatmaps which characterize the selected genomic region...
July 8, 2016: Nucleic Acids Research
Xiaoxiao Yun, Lili Xia, Bixia Tang, Hui Zhang, Feifei Li, Zhihua Zhang
Chromosome conformation capture (3C) is a biochemical technology to analyse contact frequencies between selected genomic sites in a cell population. Its recent genomic variants, e.g. Hi-C/ chromatin interaction analysis by paired-end tag (ChIA-PET), have enabled the study of nuclear organization at an unprecedented level. However, due to the inherent low resolution and ultrahigh cost of Hi-C/ChIA-PET, 3C is still the gold standard for determining interactions between given regulatory DNA elements, such as enhancers and promoters...
2016: Database: the Journal of Biological Databases and Curation
Jérôme D Robin, Andrew T Ludlow, Ryan LaRanger, Woodring E Wright, Jerry W Shay
Next Generation Sequencing (NGS) is a powerful tool that depends on loading a precise amount of DNA onto a flowcell. NGS strategies have expanded our ability to investigate genomic phenomena by referencing mutations in cancer and diseases through large-scale genotyping, developing methods to map rare chromatin interactions (4C; 5C and Hi-C) and identifying chromatin features associated with regulatory elements (ChIP-seq, Bis-Seq, ChiA-PET). While many methods are available for DNA library quantification, there is no unambiguous gold standard...
2016: Scientific Reports
Marco Antonio Mendoza-Parra, Mohamed-Ashick M Saleem, Matthias Blum, Pierre-Etienne Cholley, Hinrich Gronemeyer
The combination of massive parallel sequencing with a variety of modern DNA/RNA enrichment technologies provides means for interrogating functional protein-genome interactions (ChIP-seq), genome-wide transcriptional activity (RNA-seq; GRO-seq), chromatin accessibility (DNase-seq, FAIRE-seq, MNase-seq), and more recently the three-dimensional organization of chromatin (Hi-C, ChIA-PET). In systems biology-based approaches several of these readouts are generally cumulated with the aim of describing living systems through a reconstitution of the genome-regulatory functions...
2016: Methods in Molecular Biology
Martin Oti, Jonas Falck, Martijn A Huynen, Huiqing Zhou
BACKGROUND: The CCTC-binding factor (CTCF) protein is involved in genome organization, including mediating three-dimensional chromatin interactions. Human patient lymphocytes with mutations in a single copy of the CTCF gene have reduced expression of enhancer-associated genes involved in response to stimuli. We hypothesize that CTCF interactions stabilize enhancer-promoter chromatin interaction domains, facilitating increased expression of genes in response to stimuli. Here we systematically investigate this model using computational analyses...
2016: BMC Genomics
Yun Zhu, Zhao Chen, Kai Zhang, Mengchi Wang, David Medovoy, John W Whitaker, Bo Ding, Nan Li, Lina Zheng, Wei Wang
The human genome is tightly packaged into chromatin whose functional output depends on both one-dimensional (1D) local chromatin states and three-dimensional (3D) genome organization. Currently, chromatin modifications and 3D genome organization are measured by distinct assays. An emerging question is whether it is possible to deduce 3D interactions by integrative analysis of 1D epigenomic data and associate 3D contacts to functionality of the interacting loci. Here we present EpiTensor, an algorithm to identify 3D spatial associations within topologically associating domains (TADs) from 1D maps of histone modifications, chromatin accessibility and RNA-seq...
2016: Nature Communications
Xiaowei Xie, Wenbin Ma, Zhou Songyang, Zhenhua Luo, Junfeng Huang, Zhiming Dai, Yuanyan Xiong
Distal regulatory elements have been shown to regulate gene transcription through spatial interactions, and single nucleotide polymorphisms (SNPs) are linked with distal gene expression by spatial proximity, which helps to explain the causal role of disease-associated SNPs in non-coding region. Therefore, studies on spatial interactions between chromatin have created a new avenue for elucidating the mechanism of transcriptional regulation in disease pathogenesis. Recently, a growing number of chromatin interactions have been revealed by means of 3C, 4C, 5C, ChIA-PET and Hi-C technologies...
2016: Database: the Journal of Biological Databases and Curation
Zhonghui Tang, Oscar Junhong Luo, Xingwang Li, Meizhen Zheng, Jacqueline Jufen Zhu, Przemyslaw Szalaj, Pawel Trzaskoma, Adriana Magalska, Jakub Wlodarczyk, Blazej Ruszczycki, Paul Michalski, Emaly Piecuch, Ping Wang, Danjuan Wang, Simon Zhongyuan Tian, May Penrad-Mobayed, Laurent M Sachs, Xiaoan Ruan, Chia-Lin Wei, Edison T Liu, Grzegorz M Wilczynski, Dariusz Plewczynski, Guoliang Li, Yijun Ruan
Spatial genome organization and its effect on transcription remains a fundamental question. We applied an advanced chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) strategy to comprehensively map higher-order chromosome folding and specific chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase II (RNAPII) with haplotype specificity and nucleotide resolution in different human cell lineages. We find that CTCF/cohesin-mediated interaction anchors serve as structural foci for spatial organization of constitutive genes concordant with CTCF-motif orientation, whereas RNAPII interacts within these structures by selectively drawing cell-type-specific genes toward CTCF foci for coordinated transcription...
December 17, 2015: Cell
Xiong Ji, Daniel B Dadon, Benjamin E Powell, Zi Peng Fan, Diego Borges-Rivera, Sigal Shachar, Abraham S Weintraub, Denes Hnisz, Gianluca Pegoraro, Tong Ihn Lee, Tom Misteli, Rudolf Jaenisch, Richard A Young
In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states...
February 4, 2016: Cell Stem Cell
Nathan Harmston, Elizabeth Ing-Simmons, Malcolm Perry, Anja Barešić, Boris Lenhard
BACKGROUND: Precise quantitative and spatiotemporal control of gene expression is necessary to ensure proper cellular differentiation and the maintenance of homeostasis. The relationship between gene expression and the spatial organisation of chromatin is highly complex, interdependent and not completely understood. The development of experimental techniques to interrogate both the higher-order structure of chromatin and the interactions between regulatory elements has recently lead to important insights on how gene expression is controlled...
November 17, 2015: BMC Genomics
Nicolas Buisine, Xiaoan Ruan, Patrice Bilesimo, Alexis Grimaldi, Gladys Alfama, Pramila Ariyaratne, Fabianus Mulawadi, Jieqi Chen, Wing-Kin Sung, Edison T Liu, Barbara A Demeneix, Yijun Ruan, Laurent M Sachs
Genome-wide functional analyses require high-resolution genome assembly and annotation. We applied ChIA-PET to analyze gene regulatory networks, including 3D chromosome interactions, underlying thyroid hormone (TH) signaling in the frog Xenopus tropicalis. As the available versions of Xenopus tropicalis assembly and annotation lacked the resolution required for ChIA-PET we improve the genome assembly version 4.1 and annotations using data derived from the paired end tag (PET) sequencing technologies and approaches (e...
2015: PloS One
Ming-Chen Tsai, Yu-Chi Shu, Chia-Chen Hsu, Chih-Kung Lin, Jih-Chin Lee, Yueng-Hsiang Chu, Wen-Yen Huang
BACKGROUND: Biopsy of the retropharyngeal node is not routinely accessible. The diagnosis of retropharyngeal lymph node recurrence in patients with nasopharyngeal carcinoma (NPC) is often based on an imaging study. METHODS: We reported a patient with NPC who was incorrectly diagnosed with left retropharyngeal lymph node recurrence by both MRI and positron emission tomography (PET)/CT. RESULTS: A woman who was treated for stage IVA NPC 2 years previously was found to have a nodal lesion in the left retropharyngeal space on MRI together with focal fluorodeoxyglucose (FDG) uptake on PET/CT...
April 2016: Head & Neck
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