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chromosome conformation

Jinlei Han, Zhiliang Zhang, Kai Wang
It is well known that the chromosomes are organized in the nucleus and this spatial arrangement of genome play a crucial role in gene regulation and genome stability. Different techniques have been developed and applied to uncover the intrinsic mechanism of genome architecture, especially the chromosome conformation capture (3C) and 3C-derived methods. 3C and 3C-derived techniques provide us approaches to perform high-throughput chromatin architecture assays at the genome scale. However, the advantage and disadvantage of current methodologies of C-technologies have not been discussed extensively...
2018: Molecular Cytogenetics
Dal-Hoe Koo, William T Molin, Christopher A Saski, Jiming Jiang, Karthik Putta, Mithila Jugulam, Bernd Friebe, Bikram S Gill
Gene amplification has been observed in many bacteria and eukaryotes as a response to various selective pressures, such as antibiotics, cytotoxic drugs, pesticides, herbicides, and other stressful environmental conditions. An increase in gene copy number is often found as extrachromosomal elements that usually contain autonomously replicating extrachromosomal circular DNA molecules (eccDNAs). Amaranthus palmeri , a crop weed, can develop herbicide resistance to glyphosate [ N -(phosphonomethyl) glycine] by amplification of the 5-enolpyruvylshikimate-3-phosphate synthase ( EPSPS ) gene, the molecular target of glyphosate...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Asli Yildirim, Michael Feig
High-resolution three-dimensional models of Caulobacter crescentus nucleoid structures were generated via a multi-scale modeling protocol. Models were built as a plectonemically supercoiled circular DNA and by incorporating chromosome conformation capture based data to generate an ensemble of base pair resolution models consistent with the experimental data. Significant structural variability was found with different degrees of bending and twisting but with overall similar topologies and shapes that are consistent with C...
February 26, 2018: Nucleic Acids Research
Yong-Zhen Huang, Li-Na Qian, Jian Wang, Chun-Lei Zhang, Xing-Tang Fang, Chu-Zhao Lei, Xian-Yong Lan, Yun Ma, Yue-Yu Bai, Feng-Peng Lin, Hong Chen
The α-adducin (ADD1) is a subunit of adducin which is a cytoskeleton heterodimeric protein. Adducin participates in oocytes chromosome meiosis of mice, prompting adducin has an effect on embryonic development. Adducin gene mutation has significantly functional change. So the present study was to identify and characterize polymorphisms within the coding region of the bovine ADD1 gene among different cattle breeds. Here, 11 novel single nucleotide polymorphisms (SNPs 1-11) were identified by DNA sequencing and polymerase chain reaction-single stranded conformational polymorphism, there were one synonymous mutation in exon 1 (SNP1); four missense mutations in exons 4, 7, and 8 (SNPs 3-6); and six mutations in introns 4, 12, 13, and 14 (SNPs 2, 7-10)...
March 12, 2018: Animal Biotechnology
Philipp G Maass, A Rasim Barutcu, Catherine L Weiner, John L Rinn
Imaging (fluorescence in situ hybridization [FISH]) and genome-wide chromosome conformation capture (Hi-C) are two major approaches to the study of higher-order genome organization in the nucleus. Intra-chromosomal and inter-chromosomal interactions (referred to as non-homologous chromosomal contacts [NHCCs]) have been observed by several FISH-based studies, but locus-specific NHCCs have not been detected by Hi-C. Due to crosslinking, neither of these approaches assesses spatiotemporal properties. Toward resolving the discrepancies between imaging and Hi-C, we sought to understand the spatiotemporal properties of NHCCs in living cells by CRISPR/Cas9 live-cell imaging (CLING)...
February 27, 2018: Molecular Cell
Timothy J Stodola, Pengyuan Liu, Yong Liu, Andrew Vallejos, Aron M Geurts, Andrew S Greene, Mingyu Liang
A challenge to understanding enhancer-gene relationships is that enhancers are not always sequentially close to the gene they regulate. Physical proximity mapping through sequencing can provide an unbiased view of the chromatin close to the proximal promoter of the renin gene (Ren). Our objective was to determine genomic regions that physically interact with the renin proximal promoter, using two different genetic backgrounds, the Dahl salt sensitive and normotensive SS-13BN, which have been shown to have different regulation of plasma renin in vivo...
March 9, 2018: Physiological Genomics
Jose Luis Royo, Joan Valls, Rafael D Acemel, Carlos Gómez-Marin, Mariona Pascual-Pons, Arantxa Lupiañez, Jose Luis Gomez-Skarmeta, Joan Fibla
Previous reports have proposed that personality may have played a role on human Out-Of-Africa migration, pinpointing some genetic variants that were positively selected in the migrating populations. In this work, we discuss the role of a common copy-number variant within the SIRPB1 gene, recently associated with impulsive behavior, in the human Out-Of-Africa migration. With the analysis of the variant distribution across forty-two different populations, we found that the SIRPB1 haplotype containing duplicated allele significantly correlated with human migratory distance, being one of the few examples of positively selected loci found across the human world colonization...
2018: PloS One
Robert-Jan Palstra, Elisa de Crignis, Michael D Röling, Thomas van Staveren, Tsung Wai Kan, Wilfred van Ijcken, Yvonne M Mueller, Peter D Katsikis, Tokameh Mahmoudi
We integrated data obtained from HIV-1 genome-wide association studies with T cell-derived epigenome data and found that the noncoding intergenic variant rs4349147, which is statistically associated with HIV-1 acquisition, is located in a CD4+ T cell-specific deoxyribonuclease I hypersensitive region, suggesting regulatory potential for this variant. Deletion of the rs4349147 element in Jurkat cells strongly reduced expression of interleukin-32 (IL-32), approximately 10-kb upstream, and chromosome conformation capture assays identified a chromatin loop between rs4349147 and the IL-32 promoter validating its function as a long-distance enhancer...
February 2018: Science Advances
Quentin Szabo, Daniel Jost, Jia-Ming Chang, Diego I Cattoni, Giorgio L Papadopoulos, Boyan Bonev, Tom Sexton, Julian Gurgo, Caroline Jacquier, Marcelo Nollmann, Frédéric Bantignies, Giacomo Cavalli
Deciphering the rules of genome folding in the cell nucleus is essential to understand its functions. Recent chromosome conformation capture (Hi-C) studies have revealed that the genome is partitioned into topologically associating domains (TADs), which demarcate functional epigenetic domains defined by combinations of specific chromatin marks. However, whether TADs are true physical units in each cell nucleus or whether they reflect statistical frequencies of measured interactions within cell populations is unclear...
February 2018: Science Advances
Guillaume Combes, Helena Barysz, Chantal Garand, Luciano Gama Braga, Ibrahim Alharbi, Philippe Thebault, Luc Murakami, Dominic P Bryne, Stasa Stankovic, Patrick A Eyers, Victor M Bolanos-Garcia, William C Earnshaw, John Maciejowski, Prasad V Jallepalli, Sabine Elowe
Monopolar spindle 1 (Mps1) is a conserved apical kinase in the spindle assembly checkpoint (SAC) that ensures accurate segregation of chromosomes during mitosis. Mps1 undergoes extensive auto- and transphosphorylation, but the regulatory and functional consequences of these modifications remain unclear. Recent findings highlight the importance of intermolecular interactions between the N-terminal extension (NTE) of Mps1 and the Hec1 subunit of the NDC80 complex, which control Mps1 localization at kinetochores and activation of the SAC...
February 20, 2018: Current Biology: CB
Chen Sun, Chang Lu
Detecting three-dimensional (3D) genome organization in the form of physical interactions between various genomic loci is of great importance for understanding transcriptional regulations and cellular fate. Chromosome Conformation Capture (3C) method is the gold standard for examining chromatin organization, but usually requires a large number of cells (>107 ). This hinders studies of scarce tissue samples from animals and patients using the method. Here we developed a microfluidics-based approach for examining chromosome conformation by 3C technology...
March 2, 2018: Analytical Chemistry
Antonio F Pardiñas, Peter Holmans, Andrew J Pocklington, Valentina Escott-Price, Stephan Ripke, Noa Carrera, Sophie E Legge, Sophie Bishop, Darren Cameron, Marian L Hamshere, Jun Han, Leon Hubbard, Amy Lynham, Kiran Mantripragada, Elliott Rees, James H MacCabe, Steven A McCarroll, Bernhard T Baune, Gerome Breen, Enda M Byrne, Udo Dannlowski, Thalia C Eley, Caroline Hayward, Nicholas G Martin, Andrew M McIntosh, Robert Plomin, David J Porteous, Naomi R Wray, Armando Caballero, Daniel H Geschwind, Laura M Huckins, Douglas M Ruderfer, Enrique Santiago, Pamela Sklar, Eli A Stahl, Hyejung Won, Esben Agerbo, Thomas D Als, Ole A Andreassen, Marie Bækvad-Hansen, Preben Bo Mortensen, Carsten Bøcker Pedersen, Anders D Børglum, Jonas Bybjerg-Grauholm, Srdjan Djurovic, Naser Durmishi, Marianne Giørtz Pedersen, Vera Golimbet, Jakob Grove, David M Hougaard, Manuel Mattheisen, Espen Molden, Ole Mors, Merete Nordentoft, Milica Pejovic-Milovancevic, Engilbert Sigurdsson, Teimuraz Silagadze, Christine Søholm Hansen, Kari Stefansson, Hreinn Stefansson, Stacy Steinberg, Sarah Tosato, Thomas Werge, David A Collier, Dan Rujescu, George Kirov, Michael J Owen, Michael C O'Donovan, James T R Walters
Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total...
February 26, 2018: Nature Genetics
Jianfeng Wu, Sirui Yang, Di Yu, Wenjing Gao, Xianjun Liu, Kun Zhang, Xueqi Fu, Wanguo Bao, Kaiyu Zhang, Jiaao Yu, Liankun Sun, Shaofeng Wang
Genetic variants near the tumor necrosis factor-α-induced protein 3 gene (TNFAIP3) at the chromosomal region 6q23 demonstrated significant associations with multiple autoimmune diseases. The signals of associations have been explained to the TNFAIP3 gene, the most likely causal gene. In this study, we employed CRISPR/cas9 genome-editing tool to generate cell lines with deletions including a candidate causal variant, rs6927172, at 140 kb upstream of the TNFAIP3 gene. Interestingly, we observed alterations of multiple genes including IL-20RA encoding a subunit of the receptor for interleukin 20...
February 23, 2018: Genes and Immunity
Shankar Shastry, Olga Steinberg-Neifach, Neal Lue, Michael D Stone
Telomerase is a specialized enzyme that maintains telomere length by adding DNA repeats to chromosome ends. The catalytic protein subunit of telomerase utilizes the integral telomerase RNA to direct telomere DNA synthesis. The telomerase essential N-terminal (TEN) domain is required for enzyme function; however, the precise mechanism of the TEN domain during catalysis is not known. We report a single-molecule study of dynamic TEN-induced conformational changes in its nucleic acid substrates. The TEN domain from the yeast Candida parapsilosis (Cp) exhibits a strong binding preference for double-stranded nucleic acids, with particularly high affinity for an RNA-DNA hybrid mimicking the template-product complex...
February 21, 2018: Nucleic Acids Research
Qian Bian, Erika C Anderson, Katjuša Brejc, Barbara J Meyer
The function of chromatin modification in establishing higher-order chromosome structure during gene regulation has been elusive. We dissected the machinery and mechanism underlying the enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during Caenorhabditis elegans dosage compensation and discovered a key role for H4K20me1 in regulating X-chromosome topology and chromosome-wide gene expression. Structural and functional analysis of the dosage compensation complex (DCC) subunit DPY-21 revealed a novel Jumonji C demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals...
February 22, 2018: Cold Spring Harbor Symposia on Quantitative Biology
Oluwatosin Oluwadare, Yuxiang Zhang, Jianlin Cheng
BACKGROUND: The development of chromosomal conformation capture techniques, particularly, the Hi-C technique, has made the analysis and study of the spatial conformation of a genome an important topic in bioinformatics and computational biology. Aided by high-throughput next generation sequencing techniques, the Hi-C technique can generate genome-wide, large-scale intra- and inter-chromosomal interaction data capable of describing in details the spatial interactions within a genome. These data can be used to reconstruct 3D structures of chromosomes that can be used to study DNA replication, gene regulation, genome interaction, genome folding, and genome function...
February 23, 2018: BMC Genomics
Shuvra Shekhar Roy, Ananda Kishore Mukherjee, Shantanu Chowdhury
Over the last 15 years, development of chromosome conformation capture (3C) and its subsequent high-throughput variants in conjunction with the fast development of sequencing technology has allowed investigators to generate large volumes of data giving insights into the spatial three-dimensional (3D) architecture of the genome. This huge data has been analyzed and validated using various statistical, mathematical, genomics, and biophysical tools in order to examine the chromosomal interaction patterns, understand the organization of the chromosome, and find out functional implications of the interactions...
February 20, 2018: Human Genomics
Swati Vaish, Praveen Awasthi, Siddharth Tiwari, Shailesh Kumar Tiwari, Divya Gupta, Mahesh Kumar Basantani
Plant glutathione S-transferases are integral to normal plant metabolism, and biotic and abiotic stress tolerance. GST gene family has been characterized in diverse plant species using molecular biology and bioinformatics approaches. In the current study, in silico analysis identified 44 GSTs in Vigna radiata. Of the total 44 GSTs identified, chromosomal locations of 31 GSTs were confirmed. The pI value of GST proteins ranged from 5.10 to 9.40. The predicted molecular weights ranged from 13.12 to 50 kDa. Subcellular localization analysis revealed that all GSTs were predominantly localized in the cytoplasm...
February 15, 2018: Genome Génome / Conseil National de Recherches Canada
W Brooks
"Polyamine patterns in plasma of patients with systemic lupus erythematosus and fever" by Kim et al. provides insight into possible involvement of polyamines in systemic lupus erythematosus (SLE). The authors report decreases in N1-acetylspermidine, spermidine, spermine, and N1-acetylcadaverine and increased cadaverine in SLE. Polyamine involvement in many cellular processes and their unique characteristics (high charge, length, flexibility, and ubiquity) give polyamines importance in health and disease...
January 1, 2018: Lupus
Anandashankar Anil, Rapolas Spalinskas, Örjan Åkerborg, Pelin Sahlén, Bonnie Berger
Summary: Folding of eukaryotic genomes within nuclear space enables physical and functional contacts between regions that are otherwise kilobases away in sequence space. Targeted chromosome conformation capture methods (T2C, chi-C and HiCap) are capable of informing genomic contacts for a subset of regions targeted by probes. We here present HiCapTools, a software package that can design sequence capture probes for targeted chromosome capture applications and analyse sequencing output to detect proximities involving targeted fragments...
February 15, 2018: Bioinformatics
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