scholarly journals Ultrafine mapping of chromosome conformation at hundred basepair resolution reveals regulatory genome architecture

2019 ◽  
Author(s):  
Yizhou Zhu ◽  
Yousin Suh
Keyword(s):  
Regulatory Elements ◽  
Interaction Networks ◽  
Chromatin Interaction ◽  
Resolution Limit ◽  
Chromosome Conformation ◽  
Chromatin Interactions ◽  
Genome Wide ◽  
Regulatory Genome ◽  
Contact Domain

AbstractThe resolution limit of chromatin conformation capture methodologies (3Cs) has restrained their application in detection of fine-level chromatin structure mediated by cis-regulatory elements (CREs). Here we report two 3C-derived methods, Tri-4C and Tri-HiC, which utilize mult-restriction enzyme digestions for ultrafine mapping of targeted and genome-wide chromatin interaction, respectively, at up to one hundred basepair resolution. Tri-4C identified CRE loop interaction networks and quantifatively revealed their alterations underlying dynamic gene control. Tri-HiC uncovered global fine-gage regulatory interaction networks, identifying > 20-fold more enhancer:promoter (E:P) loops than in situ HiC. In addition to vasly improved identification of subkilobase-sized E:P loops, Tri-HiC also uncovered interaction stripes and contact domain insulation from promoters and enhancers, revealing their loop extrusion behaviors resembling the topologically-associated domain (TAD) boundaries. Tri-4C and Tri-HiC provide robust approaches to achieve the high resolution interactome maps required for characterizing fine-gage regulatory chromatin interactions in analysis of development, homeostasis and disease.

scholarly journals Candidate Cancer Driver Mutations in Distal Regulatory Elements and Long-Range Chromatin Interaction Networks

2020 ◽  
Vol 77 (6) ◽  
pp. 1307-1321.e10 ◽  
Author(s):  
Helen Zhu ◽  
Liis Uusküla-Reimand ◽  
Keren Isaev ◽  
Lina Wadi ◽  
Azad Alizada ◽  
...  
Keyword(s):  
Long Range ◽  
Regulatory Elements ◽  
Interaction Networks ◽  
Chromatin Interaction ◽  
Driver Mutations ◽  
Cancer Driver ◽  
Distal Regulatory Elements

scholarly journals The native cistrome and sequence motif families of the maize ear

PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009689
Author(s):  
Savannah D. Savadel ◽  
Thomas Hartwig ◽  
Zachary M. Turpin ◽  
Daniel L. Vera ◽  
Pei-Yau Lung ◽  
...  
Keyword(s):  
High Resolution ◽  
Binding Sites ◽  
Regulatory Networks ◽  
Regulatory Elements ◽  
Chromatin Interaction ◽  
Sequence Motif ◽  
Binding Prediction ◽  
Interaction Sites ◽  
Genome Wide ◽  
Dna Regulatory Elements

Elucidating the transcriptional regulatory networks that underlie growth and development requires robust ways to define the complete set of transcription factor (TF) binding sites. Although TF-binding sites are known to be generally located within accessible chromatin regions (ACRs), pinpointing these DNA regulatory elements globally remains challenging. Current approaches primarily identify binding sites for a single TF (e.g. ChIP-seq), or globally detect ACRs but lack the resolution to consistently define TF-binding sites (e.g. DNAse-seq, ATAC-seq). To address this challenge, we developed MNase-defined cistrome-Occupancy Analysis (MOA-seq), a high-resolution (< 30 bp), high-throughput, and genome-wide strategy to globally identify putative TF-binding sites within ACRs. We used MOA-seq on developing maize ears as a proof of concept, able to define a cistrome of 145,000 MOA footprints (MFs). While a substantial majority (76%) of the known ATAC-seq ACRs intersected with the MFs, only a minority of MFs overlapped with the ATAC peaks, indicating that the majority of MFs were novel and not detected by ATAC-seq. MFs were associated with promoters and significantly enriched for TF-binding and long-range chromatin interaction sites, including for the well-characterized FASCIATED EAR4, KNOTTED1, and TEOSINTE BRANCHED1. Importantly, the MOA-seq strategy improved the spatial resolution of TF-binding prediction and allowed us to identify 215 motif families collectively distributed over more than 100,000 non-overlapping, putatively-occupied binding sites across the genome. Our study presents a simple, efficient, and high-resolution approach to identify putative TF footprints and binding motifs genome-wide, to ultimately define a native cistrome atlas.

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 FISH-ing for captured contacts: towards reconciling FISH and 3C

2016 ◽  
Author(s):  
Geoff Fudenberg ◽  
Maxim Imakaev
Keyword(s):  
Genomic Sequence ◽  
Three Dimensions ◽  
Spatial Distance ◽  
Chromosome Conformation ◽  
One Dimensional ◽  
Genome Wide ◽  
Contact Frequency ◽  
The One ◽  
Chromosomal Loci

AbstractDeciphering how the one-dimensional information encoded in a genomic sequence is read out in three-dimensions is a pressing contemporary challenge. Chromosome conformation capture (3C) and fluorescence in-situ hybridization (FISH) are two popular technologies that provide important links between genomic sequence and 3D chromosome organization. However, how to integrate views from 3C, or genome-wide Hi-C, and FISH is far from solved. We first discuss what each of these methods measure by reconsidering available matched experimental data for Hi-C and FISH. Using polymer simulations, we then demonstrate that contact frequency is distinct from average spatial distance. We show this distinction can create a seemingly-paradoxical relationship between 3C and FISH. Finally, we consider how the measurement of specific interactions between chromosomal loci might be differentially affected by the two technologies. Together, our results have implications for future attempts to cross-validate and integrate 3C and FISH, as well as for developing models of chromosomes.

scholarly journals Chromatin interaction analysis with updated ChIA-PET Tool (V3)

2019 ◽  
Author(s):  
Guoliang Li ◽  
Tongkai Sun ◽  
Huidan Chang ◽  
Liuyang Cai ◽  
Ping Hong ◽  
...  
Keyword(s):  
Data Analysis ◽  
Target Genes ◽  
Sequence Data ◽  
Interaction Analysis ◽  
Regulatory Elements ◽  
Chromatin Interaction ◽  
Data Set ◽  
Chromatin Interactions ◽  
A Genome ◽  
Public Data

AbstractUnderstanding chromatin interactions is important since they create chromosome conformation and link the cis- and trans-regulatory elements to their target genes for transcriptional regulation. Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing is a genome-wide high-throughput technology that detects chromatin interactions associated with a specific protein of interest. Previously we developed ChIA-PET Tool in 2010 for ChIA-PET data analysis. Here we present the updated version of ChIA-PET Tool (V3), is a computational package to process the next-generation sequence data generated from ChIA-PET experiments. It processes the short-read data and long-read ChIA-PET data with multithreading and generates the statistics of results in a HTML file. In this paper, we provide a detailed demonstration of the design of ChIA-PET Tool V3 and how to install it and analyze a specific ChIA-PET data set with it. At present, other ChIA-PET data analysis tools have developed including ChiaSig, MICC, Mango and ChIA-PET2 and so on. We compared our tool with other tools using the same public data set in the same machine. Most of peaks detected by ChIA-PET Tool V3 overlap with those from other tools. There is higher enrichment for significant chromatin interactions of ChIA-PET Tool V3 in APA plot. ChIA-PET Tool V3 is open source and is available at GitHub (https://github.com/GuoliangLi-HZAU/ChIA-PET_Tool_V3/).

scholarly journals ChIA-PIPE: A fully automated pipeline for ChIA-PET data analysis and visualization

2018 ◽  
Author(s):  
Daniel Capurso ◽  
Jiahui Wang ◽  
Simon Zhongyuan Tian ◽  
Liuyang Cai ◽  
Sandeep Namburi ◽  
...  
Keyword(s):  
Specific Protein ◽  
Peak Calling ◽  
Mapping Data ◽  
Read Mapping ◽  
Contact Maps ◽  
Chromatin Interactions ◽  
Genome Wide ◽  
Allele Specific ◽  
Automated Pipeline ◽  
Contact Domain

AbstractChIA-PET enables the genome-wide discovery of chromatin interactions involving specific protein factors, with base-pair resolution. Interpreting ChIA-PET data depends on having a robust analytic pipeline. Here, we introduce ChIA-PIPE, a fully automated pipeline for ChIA-PET data processing, quality assessment, analysis, and visualization. ChIA-PIPE performs linker filtering, read mapping, peak calling, loop calling, chromatin-contact-domain calling, and can resolve allele-specific peaks and loops. ChIA-PIPE also automates quality-control assessment for each dataset. Furthermore, ChIA-PIPE generates input files for visualizing 2D contact maps with Juicebox and HiGlass, and provides a new dockerized visualization tool for high-resolution, browser-based exploration of peaks and loops. With minimal adjusting, ChIA-PIPE can also be suited for the analysis of other related chromatin-mapping data.

scholarly journals The 3D Genome Browser: a web-based browser for visualizing 3D genome organization and long-range chromatin interactions

2017 ◽  
Author(s):  
Yanli Wang ◽  
Bo Zhang ◽  
Lijun Zhang ◽  
Lin An ◽  
Jie Xu ◽  
...  
Keyword(s):  
Genome Organization ◽  
Target Genes ◽  
Genome Structure ◽  
Regulatory Elements ◽  
Genomic Region ◽  
Genome Browser ◽  
Chromatin Interaction ◽  
Interaction Data ◽  
3D Genome ◽  
Chromatin Interactions

ABSTRACTRecent advent of 3C-based technologies such as Hi-C and ChIA-PET provides us an opportunity to explore chromatin interactions and 3D genome organization in an unprecedented scale and resolution. However, it remains a challenge to visualize chromatin interaction data due to its size and complexity. Here, we introduce the 3D Genome Browser (http://3dgenome.org), which allows users to conveniently explore both publicly available and their own chromatin interaction data. Users can also seamlessly integrate other “omics” data sets, such as ChIP-Seq and RNA-Seq for the same genomic region, to gain a complete view of both regulatory landscape and 3D genome structure for any given gene. Finally, our browser provides multiple methods to link distal cis-regulatory elements with their potential target genes, including virtual 4C, ChIA-PET, Capture Hi-C and cross-cell-type correlation of proximal and distal DNA hypersensitive sites, and therefore represents a valuable resource for the study of gene regulation in mammalian genomes.

scholarly journals Epigenetic Analyses of Human Left Atrial Tissue Identifies Gene Networks Underlying Atrial Fibrillation

2020 ◽  
Vol 13 (6) ◽  
Author(s):  
Amelia Weber Hall ◽  
Mark Chaffin ◽  
Carolina Roselli ◽  
Honghuang Lin ◽  
Steven A. Lubitz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atrial Fibrillation ◽  
Molecular Mechanisms ◽  
Regulatory Elements ◽  
Genome Wide Association ◽  
Cardiac Conduction ◽  
Chromatin Interaction ◽  
Genome Wide Association Studies ◽  
Chromatin States ◽  
Genome Wide

Background: Atrial fibrillation (AF) often arises from structural abnormalities in the left atria (LA). Annotation of the noncoding genome in human LA is limited, as are effects on gene expression and chromatin architecture. Many AF-associated genetic variants reside in noncoding regions; this knowledge gap impairs efforts to understand the molecular mechanisms of AF and cardiac conduction phenotypes. Methods: We generated a model of the LA noncoding genome by profiling 7 histone post-translational modifications (active: H3K4me3, H3K4me2, H3K4me1, H3K27ac, H3K36me3; repressive: H3K27me3, H3K9me3), CTCF binding, and gene expression in samples from 5 individuals without structural heart disease or AF. We used MACS2 to identify peak regions ( P <0.01), applied a Markov model to classify regulatory elements, and annotated this model with matched gene expression data. We intersected chromatin states with expression quantitative trait locus, DNA methylation, and HiC chromatin interaction data from LA and left ventricle. Finally, we integrated genome-wide association data for AF and electrocardiographic traits to link disease-related variants to genes. Results: Our model identified 21 epigenetic states, encompassing regulatory motifs, such as promoters, enhancers, and repressed regions. Genes were regulated by proximal chromatin states; repressive states were associated with a significant reduction in gene expression ( P <2×10 −16 ). Chromatin states were differentially methylated, promoters were less methylated than repressed regions ( P <2×10 −16 ). We identified over 15 000 LA-specific enhancers, defined by homeobox family motifs, and annotated several cardiovascular disease susceptibility loci. Intersecting AF and PR genome-wide association studies loci with long-range chromatin conformation data identified a gene interaction network dominated by NKX2-5 , TBX3 , ZFHX3 , and SYNPO2L . Conclusions: Profiling the noncoding genome provides new insights into the gene expression and chromatin regulation in human LA tissue. These findings enabled identification of a gene network underlying AF; our experimental and analytic approach can be extended to identify molecular mechanisms for other cardiac diseases and traits.

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