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https://www.readbyqxmd.com/read/29224078/investigate-global-chromosomal-interaction-by-hi-c-in-human-naive-cd4-t-cells
#1
Xiangzhi Meng, Nicole Riley, Ryan Thompson, Siddhartha Sharma
Hi-C is a methodology developed to reveal chromosomal interactions from a genome-wide perspective. Here, we described a protocol for generating Hi-C sequencing libraries in resting and activated human naive CD4 T cells to investigate activation-induced chromatin structure re-arrangement in T cell activation followed by a section reviewing the general concepts of Hi-C data analysis.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29217590/a-mechanism-of-cohesin-dependent-loop-extrusion-organizes-zygotic-genome-architecture
#2
Johanna Gassler, Hugo B Brandão, Maxim Imakaev, Ilya M Flyamer, Sabrina Ladstätter, Wendy A Bickmore, Jan-Michael Peters, Leonid A Mirny, Kikuë Tachibana
Fertilization triggers assembly of higher-order chromatin structure from a condensed maternal and a naïve paternal genome to generate a totipotent embryo. Chromatin loops and domains have been detected in mouse zygotes by single-nucleus Hi-C (snHi-C), but not bulk Hi-C. It is therefore unclear when and how embryonic chromatin conformations are assembled. Here, we investigated whether a mechanism of cohesin-dependent loop extrusion generates higher-order chromatin structures within the one-cell embryo. Using snHi-C of mouse knockout embryos, we demonstrate that the zygotic genome folds into loops and domains that critically depend on Scc1-cohesin and that are regulated in size and linear density by Wapl...
December 7, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29203909/dynamic-epigenomic-landscapes-during-early-lineage-specification-in-mouse-embryos
#3
Yu Zhang, Yunlong Xiang, Qiangzong Yin, Zhenhai Du, Xu Peng, Qiujun Wang, Miguel Fidalgo, Weikun Xia, Yuanyuan Li, Zhen-Ao Zhao, Wenhao Zhang, Jing Ma, Feng Xu, Jianlong Wang, Lei Li, Wei Xie
In mammals, all somatic development originates from lineage segregation in early embryos. However, the dynamics of transcriptomes and epigenomes acting in concert with initial cell fate commitment remains poorly characterized. Here we report a comprehensive investigation of transcriptomes and base-resolution methylomes for early lineages in peri- and postimplantation mouse embryos. We found allele-specific and lineage-specific de novo methylation at CG and CH sites that led to differential methylation between embryonic and extraembryonic lineages at promoters of lineage regulators, gene bodies, and DNA-methylation valleys...
December 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29203764/3d-genome-of-multiple-myeloma-reveals-spatial-genome-disorganization-associated-with-copy-number-variations
#4
Pengze Wu, Tingting Li, Ruifeng Li, Lumeng Jia, Ping Zhu, Yifang Liu, Qing Chen, Daiwei Tang, Yuezhou Yu, Cheng Li
The Hi-C method is widely used to study the functional roles of the three-dimensional (3D) architecture of genomes. Here, we integrate Hi-C, whole-genome sequencing (WGS) and RNA-seq to study the 3D genome architecture of multiple myeloma (MM) and how it associates with genomic variation and gene expression. Our results show that Hi-C interaction matrices are biased by copy number variations (CNVs) and can be used to detect CNVs. Also, combining Hi-C and WGS data can improve the detection of translocations...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29199022/ctcf-mediated-chromatin-loops-between-promoter-and-gene-body-regulate-alternative-splicing-across-individuals
#5
Mariana Ruiz-Velasco, Manjeet Kumar, Mang Ching Lai, Pooja Bhat, Ana Belen Solis-Pinson, Alejandro Reyes, Stefan Kleinsorg, Kyung-Min Noh, Toby J Gibson, Judith B Zaugg
The CCCTC-binding factor (CTCF) is known to establish long-range DNA contacts that alter the three-dimensional architecture of chromatin, but how the presence of CTCF influences nearby gene expression is still poorly understood. Here, we analyze CTCF chromatin immunoprecipitation sequencing, RNA sequencing, and Hi-C data, together with genotypes from a healthy human cohort, and measure statistical associations between inter-individual variability in CTCF binding and alternative exon usage. We demonstrate that CTCF-mediated chromatin loops between promoters and intragenic regions are prevalent and that when exons are in physical proximity with their promoters, CTCF binding correlates with exon inclusion in spliced mRNA...
November 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/29186290/schicnorm-a-software-package-to-eliminate-systematic-biases-in-single-cell-hi-c-data
#6
Tong Liu, Zheng Wang
Summary: We build a software package scHiCNorm that uses zero-inflated and hurdle models to remove biases from single-cell Hi-C data. Our evaluations prove that our models can effectively eliminate systematic biases for single-cell Hi-C data, which better reveal cell-to-cell variances in terms of chromosomal structures. Availability: scHiCNorm is available at http://dna.cs.miami.edu/scHiCNorm/. Perl scripts are provided that can generate bias features. Pre-built bias features for human (hg19 and hg39) and mouse (mm9 and mm10) are available to download...
November 23, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29158486/bl-hi-c-is-an-efficient-and-sensitive-approach-for-capturing-structural-and-regulatory-chromatin-interactions
#7
Zhengyu Liang, Guipeng Li, Zejun Wang, Mohamed Nadhir Djekidel, Yanjian Li, Min-Ping Qian, Michael Q Zhang, Yang Chen
In human cells, DNA is hierarchically organized and assembled with histones and DNA-binding proteins in three dimensions. Chromatin interactions play important roles in genome architecture and gene regulation, including robustness in the developmental stages and flexibility during the cell cycle. Here we propose in situ Hi-C method named Bridge Linker-Hi-C (BL-Hi-C) for capturing structural and regulatory chromatin interactions by restriction enzyme targeting and two-step proximity ligation. This method improves the sensitivity and specificity of active chromatin loop detection and can reveal the regulatory enhancer-promoter architecture better than conventional methods at a lower sequencing depth and with a simpler protocol...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29149895/novel-insights-into-chromosomal-conformations-in-cancer
#8
REVIEW
Ruobing Jia, Peiwei Chai, He Zhang, Xianqun Fan
Exploring gene function is critical for understanding the complexity of life. DNA sequences and the three-dimensional organization of chromatin (chromosomal interactions) are considered enigmatic factors underlying gene function, and interactions between two distant fragments can regulate transactivation activity via mediator proteins. Thus, a series of chromosome conformation capture techniques have been developed, including chromosome conformation capture (3C), circular chromosome conformation capture (4C), chromosome conformation capture carbon copy (5C), and high-resolution chromosome conformation capture (Hi-C)...
November 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29149264/sim3c-simulation-of-hi-c-and-meta3c-proximity-ligation-sequencing-technologies
#9
Matthew Z DeMaere, Aaron E Darling
Background: Chromosome conformation capture (3C) and Hi-C DNA sequencing methods have rapidly advanced our understanding of the spatial organization of genomes and metagenomes. Many variants of these protocols have been developed, each with their own strengths. Currently there is no systematic means for simulating sequence data from this family of sequencing protocols, potentially hindering the advancement of algorithms to exploit this new datatype. Findings: We describe a computational simulator that, given simple parameters and reference genome sequences, will simulate Hi-C sequencing on those sequences...
November 15, 2017: GigaScience
https://www.readbyqxmd.com/read/29148971/convergence-of-topological-domain-boundaries-insulators-and-polytene-interbands-revealed-by-high-resolution-mapping-of-chromatin-contacts-in-the-early-drosophila-melanogaster-embryo
#10
Michael R Stadler, Jenna E Haines, Michael Eisen
High-throughput assays of three-dimensional interactions of chromosomes have shed considerable light on the structure of animal chromatin. Despite this progress, the precise physical nature of observed structures and the forces that govern their establishment remain poorly understood. Here we present high resolution Hi-C data from early Drosophila embryos. We demonstrate that boundaries between topological domains of various sizes map to DNA elements that resemble classical insulator elements: short genomic regions sensitive to DNase digestion that are strongly bound by known insulator proteins and are frequently located between divergent promoters...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29141034/structure-of-the-human-chromosome-interaction-network
#11
Sergio Sarnataro, Andrea M Chiariello, Andrea Esposito, Antonella Prisco, Mario Nicodemi
New Hi-C technologies have revealed that chromosomes have a complex network of spatial contacts in the cell nucleus of higher organisms, whose organisation is only partially understood. Here, we investigate the structure of such a network in human GM12878 cells, to derive a large scale picture of nuclear architecture. We find that the intensity of intra-chromosomal interactions is power-law distributed. Inter-chromosomal interactions are two orders of magnitude weaker and exponentially distributed, yet they are not randomly arranged along the genomic sequence...
2017: PloS One
https://www.readbyqxmd.com/read/29137603/clustertad-an-unsupervised-machine-learning-approach-to-detecting-topologically-associated-domains-of-chromosomes-from-hi-c-data
#12
Oluwatosin Oluwadare, Jianlin Cheng
BACKGROUND: With the development of chromosomal conformation capturing techniques, particularly, the Hi-C technique, the study of the spatial conformation of a genome is becoming an important topic in bioinformatics and computational biology. The Hi-C technique can generate genome-wide chromosomal interaction (contact) data, which can be used to investigate the higher-level organization of chromosomes, such as Topologically Associated Domains (TAD), i.e., locally packed chromosome regions bounded together by intra chromosomal contacts...
November 14, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29117547/a-prostate-cancer-risk-element-functions-as-a-repressive-loop-that-regulates-hoxa13
#13
Zhifei Luo, Suhn Kyong Rhie, Fides D Lay, Peggy J Farnham
Prostate cancer (PCa) is the leading cancer among men in the United States, with genetic factors contributing to ∼42% of the susceptibility to PCa. We analyzed a PCa risk region located at 7p15.2 to gain insight into the mechanisms by which this noncoding region may affect gene regulation and contribute to PCa risk. We performed Hi-C analysis and demonstrated that this region has long-range interactions with the HOXA locus, located ∼873 kb away. Using the CRISPR/Cas9 system, we deleted a 4-kb region encompassing several PCa risk-associated SNPs and performed RNA-seq to investigate transcriptomic changes in prostate cells lacking the regulatory element...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29113562/utilizing-networks-for-differential-analysis-of-chromatin-interactions
#14
Lu Liu, Jianhua Ruan
Chromatin conformation capture with high-throughput sequencing (Hi-C) is a powerful technique to detect genome-wide chromatin interactions. In this paper, we introduce two novel approaches to detect differentially interacting genomic regions between two Hi-C experiments using a network model. To make input data from multiple experiments comparable, we propose a normalization strategy guided by network topological properties. We then devise two measurements, using local and global connectivity information from the chromatin interaction networks, respectively, to assess the interaction differences between two experiments...
October 19, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/29106613/3div-a-3d-genome-interaction-viewer-and-database
#15
Dongchan Yang, Insu Jang, Jinhyuk Choi, Min-Seo Kim, Andrew J Lee, Hyunwoong Kim, Junghyun Eom, Dongsup Kim, Inkyung Jung, Byungwook Lee
Three-dimensional (3D) chromatin structure is an emerging paradigm for understanding gene regulation mechanisms. Hi-C (high-throughput chromatin conformation capture), a method to detect long-range chromatin interactions, allows extensive genome-wide investigation of 3D chromatin structure. However, broad application of Hi-C data have been hindered by the level of complexity in processing Hi-C data and the large size of raw sequencing data. In order to overcome these limitations, we constructed a database named 3DIV (a 3D-genome Interaction Viewer and database) that provides a list of long-range chromatin interaction partners for the queried locus with genomic and epigenomic annotations...
November 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29099269/a-meeting-at-risk-unrepaired-dsbs-go-for-broke
#16
Aude Guénolé, Gaëlle Legube
Translocations are dramatic genomic rearrangements due to aberrant rejoining of distant DNA ends that can trigger cancer onset and progression. Translocations frequently occur in genes, yet the mechanisms underlying their formation remain poorly understood. One potential mechanism involves DNA Double Strand Break mobility and juxtaposition (i.e. clustering), an event that has been intensively debated over the past decade. Using Capture Hi-C, we recently found that DSBs do in fact cluster in human nuclei but only when induced in transcriptionally active genes...
November 3, 2017: Nucleus
https://www.readbyqxmd.com/read/29094699/two-independent-modes-of-chromatin-organization-revealed-by-cohesin-removal
#17
Wibke Schwarzer, Nezar Abdennur, Anton Goloborodko, Aleksandra Pekowska, Geoffrey Fudenberg, Yann Loe-Mie, Nuno A Fonseca, Wolfgang Huber, Christian H Haering, Leonid Mirny, Francois Spitz
Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes...
November 2, 2017: Nature
https://www.readbyqxmd.com/read/29089515/chromatin-interaction-networks-revealed-unique-connectivity-patterns-of-broad-h3k4me3-domains-and-super-enhancers-in-3d-chromatin
#18
Asa Thibodeau, Eladio J Márquez, Dong-Guk Shin, Paola Vera-Licona, Duygu Ucar
Broad domain promoters and super enhancers are regulatory elements that govern cell-specific functions and harbor disease-associated sequence variants. These elements are characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for super enhancers and H3K4me3 for broad domains, however little is known about how they interact with each other and the rest of the genome in three-dimensional chromatin space. Using network theory methods, we studied chromatin interactions between broad domains and super enhancers in three ENCODE cell lines (K562, MCF7, GM12878) obtained via ChIA-PET, Hi-C, and Hi-CHIP assays...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29081791/physical-interactions-and-expression-quantitative-traits-loci-identify-regulatory-connections-for-obesity-and-type-2-diabetes-associated-snps
#19
Tayaza Fadason, Cameron Ekblad, John R Ingram, William S Schierding, Justin M O'Sullivan
The mechanisms that underlie the association between obesity and type 2 diabetes are not fully understood. Here, we investigated the role of the 3D genome organization in the pathogeneses of obesity and type-2 diabetes. We interpreted the combined and differential impacts of 196 diabetes and 390 obesity associated single nucleotide polymorphisms (SNPs) by integrating data on the genes with which they physically interact (as captured by Hi-C) and the functional [i.e., expression quantitative trait loci (eQTL)] outcomes associated with these interactions...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29080874/-computer-methods-of-analysis-of-chromosome-contacts-in-the-cell-nucleus-based-on-sequencing-technology-data
#20
Y L Orlov, O Thierry, A G Bogomolov, A V Tsukanov, E V Kulakova, E R Galieva, A O Bragin, G Li
The study spatial chromosome structure and chromosome folding in the interphase cell nucleus is an important challenge of world science. Detection of eukaryotic genome regions that physically interact with each other could be done by modern sequencing technologies. A basic method of chromosome folding by total sequencing of contacting DNA fragments is HI-C. Long-range chromosomal interactions play an important role in gene transcription and regulation. The study of chromosome interactions, 3D (three-dimensional) genome structure and its effect on gene transcription allows revealing fundamental biological processes from a viewpoint of structural regulation and are important for cancer research...
October 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
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