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https://www.readbyqxmd.com/read/29772275/5c-id-increased-resolution-chromosome-conformation-capture-carbon-copy-with-in-situ-3c-and-double-alternating-primer-design
#1
Ji Hun Kim, Katelyn R Titus, Wanfeng Gong, Jonathan A Beagan, Zhendong Cao, Jennifer E Phillips-Cremins
Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs, and looping interactions. Currently, there is a great need to evaluate the link between chromatin topology and genome function across many biological conditions and genetic perturbations. Hi-C can generate genome-wide maps of looping interactions but is intractable for high-throughput comparison of loops across multiple conditions due to the enormous number of reads (>6 Billion) required per library...
May 14, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29771388/gwas4d-multidimensional-analysis-of-context-specific-regulatory-variant-for-human-complex-diseases-and-traits
#2
Dandan Huang, Xianfu Yi, Shijie Zhang, Zhanye Zheng, Panwen Wang, Chenghao Xuan, Pak Chung Sham, Junwen Wang, Mulin Jun Li
Genome-wide association studies have generated over thousands of susceptibility loci for many human complex traits, and yet for most of these associations the true causal variants remain unknown. Tissue/cell type-specific prediction and prioritization of non-coding regulatory variants will facilitate the identification of causal variants and underlying pathogenic mechanisms for particular complex diseases and traits. By leveraging recent large-scale functional genomics/epigenomics data, we develop an intuitive web server, GWAS4D (http://mulinlab...
May 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29767669/identification-of-mutations-in-patients-with-acquired-pure-red-cell-aplasia
#3
Xinchao Zhang, Yi Shi, Lingjun Song, Chang Shen, Qi Cai, Zhou Zhang, Jun Wu, Guohui Fu, Weiwei Shen
Idiopathic acquired pure red cell aplasia (PRCA) is a rare, autoimmune-related disease. This study aimed to describe the previously unidentified DNA alterations associated with PRCA. Here, next generation sequencing using a panel containing 295 critical genes was applied to detect potentially pathogenic mutations in four patients with PRCA. A total of 529 mutations were identified and further classified into three categories, namely, uncertain (n = 25), likely benign (n = 20) and benign (n = 484) mutations, based on the American College of Medical Genetics and Genomics (ACMG) 2015 guidelines and ClinVar database...
May 15, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29755580/finding-local-genome-rearrangements
#4
Pijus Simonaitis, Krister M Swenson
Background: The double cut and join (DCJ) model of genome rearrangement is well studied due to its mathematical simplicity and power to account for the many events that transform gene order. These studies have mostly been devoted to the understanding of minimum length scenarios transforming one genome into another. In this paper we search instead for rearrangement scenarios that minimize the number of rearrangements whose breakpoints are unlikely due to some biological criteria. One such criterion has recently become accessible due to the advent of the Hi-C experiment, facilitating the study of 3D spacial distance between breakpoint regions...
2018: Algorithms for Molecular Biology: AMB
https://www.readbyqxmd.com/read/29745835/graphteams-a-method-for-discovering-spatial-gene-clusters-in-hi-c-sequencing-data
#5
Tizian Schulz, Jens Stoye, Daniel Doerr
BACKGROUND: Hi-C sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes. We use data obtained from Hi-C experiments to provide new evidence for the existence of spatial gene clusters. These are sets of genes with associated functionality that exhibit close proximity to each other in the spatial conformation of chromosomes across several related species. RESULTS: We present the first gene cluster model capable of handling spatial data...
May 8, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29735606/allele-specific-control-of-replication-timing-and-genome-organization-during-development
#6
Juan Carlos Rivera-Mulia, Andrew Dimond, Daniel Vera, Claudia Trevilla-Garcia, Takayo Sasaki, Jared Zimmerman, Catherine Dupont, Joost Gribnau, Peter Fraser, David M Gilbert
DNA replication occurs in a defined temporal order known as the replication-timing (RT) program. RT is regulated during development in discrete chromosomal units, coordinated with transcriptional activity and 3D genome organization. Here, we derived distinct cell types from F1 hybrid musculus X castaneus mouse crosses and exploited the high single nucleotide polymorphism (SNP) density to characterize allelic differences in RT (Repli-seq), genome organization (Hi-C and promoter-capture Hi-C), gene expression (total nuclear RNA-seq) and chromatin accessibility (ATAC-seq)...
May 7, 2018: Genome Research
https://www.readbyqxmd.com/read/29728444/emerging-evidence-of-chromosome-folding-by-loop-extrusion
#7
Geoffrey Fudenberg, Nezar Abdennur, Maxim Imakaev, Anton Goloborodko, Leonid A Mirny
Chromosome organization poses a remarkable physical problem with many biological consequences: How can molecular interactions between proteins at the nanometer scale organize micron-long chromatinized DNA molecules, insulating or facilitating interactions between specific genomic elements? The mechanism of active loop extrusion holds great promise for explaining interphase and mitotic chromosome folding, yet remains difficult to assay directly. We discuss predictions from our polymer models of loop extrusion with barrier elements and review recent experimental studies that provide strong support for loop extrusion, focusing on perturbations to CTCF and cohesin assayed via Hi-C in interphase...
May 4, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29723572/iteratively-improving-hi-c-experiments-one-step-at-a-time
#8
Rosela Golloshi, Jacob Sanders, Rachel Patton McCord
The 3D organization of eukaryotic chromosomes affects key processes such as gene expression, DNA replication, cell division, and response to DNA damage. The genome-wide chromosome conformation capture (Hi-C) approach can characterize the landscape of 3D genome organization by measuring interaction frequencies between all genomic regions. Hi-C protocol improvements and rapid advances in DNA sequencing power have made Hi-C useful to study diverse biological systems, not only to elucidate the role of 3D genome structure in proper cellular function, but also to characterize genomic rearrangements, assemble new genomes, and consider chromatin interactions as potential biomarkers for diseases...
April 30, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29717274/detecting-epistasis-within-chromatin-regulatory-circuitry-reveals-cand2-as-a-novel-susceptibility-gene-for-obesity
#9
Shan-Shan Dong, Shi Yao, Yi-Xiao Chen, Yan Guo, Yu-Jie Zhang, Hui-Min Niu, Ruo-Han Hao, Hui Shen, Qing Tian, Hong-Wen Deng, Tie-Lin Yang
BACKGROUND: Genome-wide association studies have identified many susceptibility loci for obesity. However, missing heritability problem is still challenging and ignorance of genetic interactions is believed to be an important cause. Current methods for detecting interactions usually do not consider regulatory elements in non-coding regions. Interaction analyses within chromatin regulatory circuitry may identify new susceptibility loci. METHODS: We developed a pipeline named interaction analyses within chromatin regulatory circuitry (IACRC), to identify genetic interactions impacting body mass index (BMI)...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29706548/the-energetics-and-physiological-impact-of-cohesin-extrusion
#10
Laura Vian, Aleksandra Pękowska, Suhas S P Rao, Kyong-Rim Kieffer-Kwon, Seolkyoung Jung, Laura Baranello, Su-Chen Huang, Laila El Khattabi, Marei Dose, Nathanael Pruett, Adrian L Sanborn, Andres Canela, Yaakov Maman, Anna Oksanen, Wolfgang Resch, Xingwang Li, Byoungkoo Lee, Alexander L Kovalchuk, Zhonghui Tang, Steevenson Nelson, Michele Di Pierro, Ryan R Cheng, Ido Machol, Brian Glenn St Hilaire, Neva C Durand, Muhammad S Shamim, Elena K Stamenova, José N Onuchic, Yijun Ruan, Andre Nussenzweig, David Levens, Erez Lieberman Aiden, Rafael Casellas
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA...
April 24, 2018: Cell
https://www.readbyqxmd.com/read/29706538/hmgb2-loss-upon-senescence-entry-disrupts-genomic-organization-and-induces-ctcf-clustering-across-cell-types
#11
Anne Zirkel, Milos Nikolic, Konstantinos Sofiadis, Jan-Philipp Mallm, Chris A Brackley, Henrike Gothe, Oliver Drechsel, Christian Becker, Janine Altmüller, Natasa Josipovic, Theodore Georgomanolis, Lilija Brant, Julia Franzen, Mirjam Koker, Eduardo G Gusmao, Ivan G Costa, Roland T Ullrich, Wolfgang Wagner, Vassilis Roukos, Peter Nürnberg, Davide Marenduzzo, Karsten Rippe, Argyris Papantonis
Processes like cellular senescence are characterized by complex events giving rise to heterogeneous cell populations. However, the early molecular events driving this cascade remain elusive. We hypothesized that senescence entry is triggered by an early disruption of the cells' three-dimensional (3D) genome organization. To test this, we combined Hi-C, single-cell and population transcriptomics, imaging, and in silico modeling of three distinct cells types entering senescence. Genes involved in DNA conformation maintenance are suppressed upon senescence entry across all cell types...
April 20, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29700484/computational-3d-genome-modeling-using-chrom3d
#12
Jonas Paulsen, Tharvesh Moideen Liyakat Ali, Philippe Collas
Chrom3D is a computational platform for 3D genome modeling that simulates the spatial positioning of chromosome domains relative to each other and relative to the nuclear periphery. In Chrom3D, chromosomes are modeled as chains of contiguous beads, in which each bead represents a genomic domain. In this protocol, a bead represents a topologically associated domain (TAD) mapped from ensemble Hi-C data. Chrom3D takes as input data significant pairwise TAD-TAD interactions determined from a Hi-C contact matrix, and TAD interactions with the nuclear periphery, determined by ChIP-sequencing of nuclear lamins to define lamina-associated domains (LADs)...
May 2018: Nature Protocols
https://www.readbyqxmd.com/read/29700467/digestion-ligation-only-hi-c-is-an-efficient-and-cost-effective-method-for-chromosome-conformation-capture
#13
Da Lin, Ping Hong, Siheng Zhang, Weize Xu, Muhammad Jamal, Keji Yan, Yingying Lei, Liang Li, Yijun Ruan, Zhen F Fu, Guoliang Li, Gang Cao
Chromosome conformation capture (3C) technologies can be used to investigate 3D genomic structures. However, high background noise, high costs, and a lack of straightforward noise evaluation in current methods impede the advancement of 3D genomic research. Here we developed a simple digestion-ligation-only Hi-C (DLO Hi-C) technology to explore the 3D landscape of the genome. This method requires only two rounds of digestion and ligation, without the need for biotin labeling and pulldown. Non-ligated DNA was efficiently removed in a cost-effective step by purifying specific linker-ligated DNA fragments...
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29690904/ocean-c-mapping-hubs-of-open-chromatin-interactions-across-the-genome-reveals-gene-regulatory-networks
#14
Tingting Li, Lumeng Jia, Yong Cao, Qing Chen, Cheng Li
We develop a method called open chromatin enrichment and network Hi-C (OCEAN-C) for antibody-independent mapping of global open chromatin interactions. By integrating FAIRE-seq and Hi-C, OCEAN-C detects open chromatin interactions enriched by active cis-regulatory elements. We identify more than 10,000 hubs of open chromatin interactions (HOCIs) in human cells, which are mainly active promoters and enhancers bound by many DNA-binding proteins and form interaction networks crucial for gene transcription. In addition to identifying large-scale topological structures, including topologically associated domains and A/B compartments, OCEAN-C can detect HOCI-mediated chromatin interactions that are strongly associated with gene expression, super-enhancers, and broad H3K4me3 domains...
April 24, 2018: Genome Biology
https://www.readbyqxmd.com/read/29686798/computational-methods-for-assessing-chromatin-hierarchy
#15
REVIEW
Pearl Chang, Moloya Gohain, Ming-Ren Yen, Pao-Yang Chen
The hierarchical organization of chromatin is known to associate with diverse cellular functions; however, the precise mechanisms and the 3D structure remain to be determined. With recent advances in high-throughput next generation sequencing (NGS) techniques, genome-wide profiling of chromatin structures is made possible. Here, we provide a comprehensive overview of NGS-based methods for profiling "higher-order" and "primary-order" chromatin structures from both experimental and computational aspects...
2018: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/29685368/principles-of-chromosome-architecture-revealed-by-hi-c
#16
REVIEW
Kyle P Eagen
Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops...
April 20, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29684640/three-invariant-hi-c-interaction-patterns-applications-to-genome-assembly
#17
Sivan Oddes, Aviv Zelig, Noam Kaplan
Assembly of reference-quality genomes from next-generation sequencing data is a key challenge in genomics. Recently, we and others have shown that Hi-C data can be used to address several outstanding challenges in the field of genome assembly. This principle has since been developed in academia and industry, and has been used in the assembly of several major genomes. In this paper, we explore the central principles underlying Hi-C-based assembly approaches, by quantitatively defining and characterizing three invariant Hi-C interaction patterns on which these approaches can build: Intrachromosomal interaction enrichment, distance-dependent interaction decay and local interaction smoothness...
April 20, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29674753/combining-fluorescence-imaging-with-hi-c-to-study-3d-genome-architecture-of-the-same-single-cell
#18
David Lando, Srinjan Basu, Tim J Stevens, Andy Riddell, Kai J Wohlfahrt, Yang Cao, Wayne Boucher, Martin Leeb, Liam P Atkinson, Steven F Lee, Brian Hendrich, Dave Klenerman, Ernest D Laue
Fluorescence imaging and chromosome conformation capture assays such as Hi-C are key tools for studying genome organization. However, traditionally, they have been carried out independently, making integration of the two types of data difficult to perform. By trapping individual cell nuclei inside a well of a 384-well glass-bottom plate with an agarose pad, we have established a protocol that allows both fluorescence imaging and Hi-C processing to be carried out on the same single cell. The protocol identifies 30,000-100,000 chromosome contacts per single haploid genome in parallel with fluorescence images...
May 2018: Nature Protocols
https://www.readbyqxmd.com/read/29669733/evolution-of-dnaasei-hypersensitive-sites-in-mhc-regulatory-regions-of-primates
#19
Yabin Jin, Rachel M Gittelman, Yueer Lu, Xiaohui Liu, Ming D Li, Fei Ling, Joshua M Akey
It has been challenged to determine the disease-causing variant(s) for most major histocompatibility complex (MHC) associated diseases. However, it is becoming increasingly clear that regulatory variation is pervasive and a fundamentally important mechanism governing phenotypic diversity and disease susceptibility. We leveraged DNase I data from 136 human cells to characterize the regulatory landscape of the MHC region, including 4867 DNase I hypersensitive sites (DHSs). We identified thousands of regulatory elements that have been gained or lost in the human or chimpanzee genomes since their evolutionary divergence...
April 18, 2018: Genetics
https://www.readbyqxmd.com/read/29666371/integration-of-human-adipocyte-chromosomal-interactions-with-adipose-gene-expression-prioritizes-obesity-related-genes-from-gwas
#20
David Z Pan, Kristina M Garske, Marcus Alvarez, Yash V Bhagat, James Boocock, Elina Nikkola, Zong Miao, Chelsea K Raulerson, Rita M Cantor, Mete Civelek, Craig A Glastonbury, Kerrin S Small, Michael Boehnke, Aldons J Lusis, Janet S Sinsheimer, Karen L Mohlke, Markku Laakso, Päivi Pajukanta, Arthur Ko
Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression...
April 17, 2018: Nature Communications
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