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Genome Research

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https://www.readbyqxmd.com/read/28341774/rna-dna-hybrid-r-loop-immunoprecipitation-mapping-an-analytical-workflow-to-evaluate-inherent-biases
#1
László Halász, Zsolt Karányi, Beáta Boros-Oláh, Tímea Rózsa, Éva Sipos, Éva Nagy, Ágnes Mosolygó-L, Anett Mázló, Éva Rajnavölgyi, Gábor Halmos, Lóránt Székvölgyi
The impact of R-loops on the physiology and pathology of chromosomes has been demonstrated extensively by chromatin biology research. The progress in this field has been driven by technological advancement of R-loop mapping methods that largely relied on a single approach, DNA-RNA immunoprecipitation (DRIP). Most of the DRIP protocols use the experimental design that was developed by a few laboratories, without paying attention to the potential caveats that might affect the outcome of RNA-DNA hybrid mapping...
March 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28341773/pml-protein-organizes-heterochromatin-domains-where-it-regulates-histone-h3-3-deposition-by-atrx-daxx
#2
Erwan Delbarre, Kristina Ivanauskiene, Jane Spirkoski, Akshay Shah, Kristin Vekterud, Jan Øivind Moskaug, Stig Ove Bøe, Lee Wong, Thomas Küntziger, Philippe Collas
Maintenance of chromatin homeostasis involves proper delivery of histone variants to the genome. The interplay between different chaperones regulating the supply of histone variants to distinct chromatin domains is largely undeciphered. We report here a role of promyelocytic leukemia (PML) protein in routing histone variant H3.3 to chromatin and in the organization of megabase-size heterochromatic PML-associated domains which we call PADs. Loss of PML alters the heterochromatic state of PADs by shifting the histone H3 methylation balance from K9me3 to K27me3...
March 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28341772/diurnal-regulation-of-rna-polymerase-iii-transcription-is-under-the-control-of-both-the-feeding-fasting-response-and-the-circadian-clock
#3
François Mange, Viviane Praz, Eugenia Migliavacca, Ian M Willis, Frédéric Schütz, Nouria Hernandez
RNA polymerase III (pol III) synthesizes short non-coding RNAs, many of which are essential for translation. Accordingly, pol III activity is tightly regulated with cell growth and proliferation by factors such as MYC, RB1, TRP53, and MAF1. MAF1 is a repressor of pol III transcription whose activity is controlled by phosphorylation; in particular, it is inactivated through phosphorylation by the TORC1 kinase complex, a sensor of nutrient availability. Pol III regulation is thus sensitive to environmental cues, yet a diurnal profile of pol III transcription activity is so far lacking...
March 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28341771/small-chromosomal-regions-position-themselves-autonomously-according-to-their-chromatin-class
#4
Harmen Jan George van de Werken, Josien C de Haan, Yana Feodorova, Dominika Bijos, An Weuts, Koen Theunis, Sjoerd Holwerda, Wouter Meuleman, Ludo Pagie, Katharina Thanisch, Parveen Kumar, Heinrich Leonhardt, Peter Marynen, Bas van Steesel, Thierry Voet, Wouter de Laat, Irina Solovei, Boris Joffe
The spatial arrangement of chromatin is linked to the regulation of nuclear processes. One striking aspect of nuclear organization is the spatial segregation of heterochromatic and euchromatic domains. The mechanisms of this chromatin segregation are still poorly understood. In this work we investigated the link between the primary genomic sequence and chromatin domains. We analyzed the spatial intranuclear arrangement of a human artificial chromosome (HAC) in a xenospecific mouse background in comparison to an orthologous region of native mouse chromosome...
March 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28336543/in-vivo-binding-of-prdm9-reveals-interactions-with-noncanonical-genomic-sites
#5
Corinne Grey, Julie A J Clément, Jérôme Buard, Benjamin Leblanc, Ivo Gut, Marta Gut, Laurent Duret, Bernard de Massy
In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner...
March 23, 2017: Genome Research
https://www.readbyqxmd.com/read/28330902/regulation-of-nucleosome-positioning-by-a-chd-type-iii-chromatin-remodeler-and-its-relationship-to-developmental-gene-expression-in-dictyostelium
#6
James L Platt, Nicholas A Kent, Alan R Kimmel, Adrian J Harwood
Nucleosome placement and repositioning can direct transcription of individual genes; however, the precise interactions of these events are complex and largely unresolved at the whole-genome level. The Chromodomain-Helicase-DNA binding (CHD) Type III proteins are a subfamily of SWI2/SNF2 proteins that control nucleosome positioning and are associated with several complex human disorders, including CHARGE syndrome and autism. Type III CHDs are required for multicellular development of animals and Dictyostelium but are absent in plants and yeast...
March 22, 2017: Genome Research
https://www.readbyqxmd.com/read/28325850/phenotypic-diversity-and-genotypic-flexibility-of-burkholderia-cenocepacia-during-long-term-chronic-infection-of-cystic-fibrosis-lungs
#7
Amy Huei-Yi Lee, Stephane Flibotte, Sunita Sinha, Adrianna Paiero, Rachel L Ehrlich, Sergey Balashov, Garth D Ehrlich, James E A Zlosnik, Joshua Chang Mell, Corey Nislow
Chronic bacterial infections of the lung are the leading cause of morbidity and mortality in cystic fibrosis patients. Tracking bacterial evolution during chronic infections can provide insights into how host selection pressures-including immune responses and therapeutic interventions-shape bacterial genomes. We carried out genomic and phenotypic analyses of 215 serially collected Burkholderia cenocepacia isolates from 16 cystic fibrosis patients, spanning a period of 2-20 yr and a broad range of epidemic lineages...
March 21, 2017: Genome Research
https://www.readbyqxmd.com/read/28320919/pan-cancer-analysis-distinguishes-transcriptional-changes-of-aneuploidy-from-proliferation
#8
Christopher Buccitelli, Lorena Salgueiro, Konstantina Rowald, Rocio Sotillo, Balca R Mardin, Jan O Korbel
Patterns of gene expression in tumors can arise as a consequence of or result in genomic instability, characterized by the accumulation of somatic copy number alterations (SCNAs) and point mutations (PMs). Expression signatures have been widely used as markers for genomic instability, and both SCNAs and PMs could be thought to associate with distinct signatures given their different formation mechanisms. Here we test this notion by systematically investigating SCNA, PM, and transcriptome data from 2660 cancer patients representing 11 tumor types...
March 20, 2017: Genome Research
https://www.readbyqxmd.com/read/28320918/hinge-long-read-assembly-achieves-optimal-repeat-resolution
#9
Govinda M Kamath, Ilan Shomorony, Fei Xia, Thomas Courtade, David N Tse
Long-read sequencing technologies have potential to produce gold-standard de novo genome assemblies, but fully exploiting error-prone reads to resolve repeats remains a challenge. Aggressive approaches to repeat resolution often produce mis-assemblies, and conservative approaches lead to unnecessary fragmentation. We present HINGE, an assembler that achieves optimal repeat resolution by distinguishing repeats that can be resolved given the data from those that cannot. This is accomplished by adding "hinges" to reads for constructing an overlap graph where only unresolvable repeats are merged...
March 20, 2017: Genome Research
https://www.readbyqxmd.com/read/28302734/time-dependent-genetic-effects-on-gene-expression-implicate-aging-processes
#10
Julien Bryois, Alfonso Buil, Pedro G Ferreira, Nikolaos I Panousis, Andrew A Brown, Ana Viñuela, Alexandra Planchon, Deborah Bielser, Kerrin Small, Tim Spector, Emmanouil T Dermitzakis
Gene expression is dependent on genetic and environmental factors. In the last decade, a large body of research has significantly improved our understanding of the genetic architecture of gene expression. However, it remains unclear whether genetic effects on gene expression remain stable over time. Here, we show, using longitudinal whole-blood gene expression data from a twin cohort, that the genetic architecture of a subset of genes is unstable over time. In addition, we identified 2213 genes differentially expressed across time points that we linked with aging within and across studies...
March 16, 2017: Genome Research
https://www.readbyqxmd.com/read/28298431/canu-scalable-and-accurate-long-read-assembly-via-adaptive-k-mer-weighting-and-repeat-separation
#11
Sergey Koren, Brian P Walenz, Konstantin Berlin, Jason R Miller, Nicholas H Bergman, Adam M Phillippy
Long-read single-molecule sequencing has revolutionized de novo genome assembly and enabled the automated reconstruction of reference-quality genomes. However, given the relatively high error rates of such technologies, efficient and accurate assembly of large repeats and closely related haplotypes remains challenging. We address these issues with Canu, a successor of Celera Assembler that is specifically designed for noisy single-molecule sequences. Canu introduces support for nanopore sequencing, halves depth-of-coverage requirements, and improves assembly continuity while simultaneously reducing runtime by an order of magnitude on large genomes versus Celera Assembler 8...
March 15, 2017: Genome Research
https://www.readbyqxmd.com/read/28298430/metaspades-a-new-versatile-metagenomic-assembler
#12
Sergey Nurk, Dmitry Meleshko, Anton Korobeynikov, Pavel A Pevzner
While metagenomics has emerged as a technology of choice for analyzing bacterial populations, as-sembly of metagenomic data remains challenging thus stifling biological discoveries. Moreover, re-cent studies revealed that complex bacterial populations may be composed from dozens of related strains thus further amplifying the challenge metagenomic assembly. metaSPAdes addresses various challenges of metagenomic assembly by capitalizing on computational ideas that proved to be useful in assemblies of single cells and highly polymorphic diploid genomes...
March 15, 2017: Genome Research
https://www.readbyqxmd.com/read/28298429/speciation-network-in-laurasiatheria-retrophylogenomic-signals
#13
Liliya Doronina, Gennady Churakov, Andrej Kuritzin, Jingjing Shi, Robert Baertsch, Hiram Clawson, Juergen Schmitz
Rapid species radiation due to adaptive changes or occupation of new ecospaces challenges our understanding of ancestral speciation and the relationships of modern species. At the molecular level, rapid radiation with successive speciations over short time periods - too short to fix polymorphic alleles - is described as incomplete lineage sorting. Incomplete lineage sorting leads to random fixation of genetic markers and hence random signals of relationships in phylogenetic reconstructions. The situation is further complicated when you consider that the genome is a mosaic of ancestral and modern incompletely sorted sequence blocks that leads to reconstructed affiliations to one or the other relatives depending on the fixation of their shared ancestral polymorphic alleles...
March 15, 2017: Genome Research
https://www.readbyqxmd.com/read/28235832/one-thousand-somatic-snvs-per-skin-fibroblast-cell-set-baseline-of-mosaic-mutational-load-with-patterns-that-suggest-proliferative-origin
#14
Alexej Abyzov, Livia Tomasini, Bo Zhou, Nikolaos Vasmatzis, Gianfilippo Coppola, Mariangela Amenduni, Reenal Pattni, Michael Wilson, Mark Gerstein, Sherman Weissman, Alexander E Urban, Flora M Vaccarino
Few studies have been conducted to understand post-zygotic accumulation of mutations in cells of the healthy human body. We reprogrammed 32 skin fibroblast cells from families of donors into human induced pluripotent stem cell (hiPSC) lines. The clonal nature of hiPSC lines allows a high-resolution analysis of the genomes of the founder fibroblast cells without being confounded by the artifacts of single-cell whole-genome amplification. We estimate that on average a fibroblast cell in children has 1035 mostly benign mosaic SNVs...
February 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28232479/critical-threshold-levels-of-dna-methyltransferase-1-are-required-to-maintain-dna-methylation-across-the-genome-in-human-cancer-cells
#15
Yi Cai, Hsing-Chen Tsai, Ray-Whay Chiu Yen, Yang W Zhang, Xiangqian Kong, Wei Wang, Limin Xia, Stephen B Baylin
Reversing DNA methylation abnormalities and associated gene silencing, through inhibiting DNA methyltransferases (DNMTs) is an important potential cancer therapy paradigm. Maximizing this potential requires defining precisely how these enzymes maintain genome-wide, cancer specific DNA methylation. To date, there is incomplete understanding of precisely how the three DNMTs, 1, 3A, and 3B, interact for maintaining DNA methylation abnormalities in cancer. By combining genetic and shRNA depletion strategies, we define not only a dominant role for DNA methyltransferase 1 (DNMT1) but also distinct roles of 3A and 3B in genome wide DNA methylation maintenance...
February 23, 2017: Genome Research
https://www.readbyqxmd.com/read/28232478/abyss-2-0-resource-efficient-assembly-of-large-genomes-using-a-bloom-filter
#16
Shaun D Jackman, Benjamin P Vandervalk, Hamid Mohamadi, Justin Chu, Sarah Yeo, S Austin Hammond, Golnaz Jahesh, Hamza Khan, Lauren Coombe, René L Warren, Inanc Birol
The assembly of DNA sequences de novo is fundamental to genomics research. It is the first of many steps towards elucidating and characterizing whole genomes. Downstream applications, including analysis of genomic variation between species, between or within individuals critically depend on robustly assembled sequences. In the span of a single decade, the sequence throughput of leading DNA sequencing instruments has increased drastically, and coupled with established and planned large-scale, personalized medicine initiatives to sequence genomes in the thousands and even millions, the development of efficient, scalable and accurate bioinformatics tools for producing high-quality reference draft genomes is timely...
February 23, 2017: Genome Research
https://www.readbyqxmd.com/read/28223401/transcriptome-analyses-of-rhesus-monkey-pre-implantation-embryos-reveal-a-reduced-capacity-for-dna-double-strand-break-repair-in-primate-oocytes-and-early-embryos
#17
Xinyi Wang, Denghui Liu, Dajian He, Shengbo Suo, Xian Xia, Xiechao He, Jing-Dong Han, Ping Zheng
Pre-implantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell fate commitment, most of which remain mechanistically unclear in primates. In addition, primates display a high rate of embryo wastage without any clear molecular basis. Understanding the factors involved in genome reprogramming and ZGA will help the generation of induced pluripotent stem cells with high efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution...
February 21, 2017: Genome Research
https://www.readbyqxmd.com/read/28223400/distal-cpg-islands-can-serve-as-alternative-promoters-to-transcribe-genes-with-silenced-proximal-promoters
#18
Shrutii Sarda, Avinash Das, Charles Vinson, Sridhar Hannenhalli
DNA methylation at the promoter of a gene is presumed to render it silent, yet a sizable fraction of genes with methylated proximal promoters exhibit elevated expression. Here, we show, through extensive analysis of the methylome and transcriptome in 34 tissues, that in many such cases, transcription is initiated by a distal upstream CpG island (CGI) located several kilobases away that functions as an alternative promoter. Specifically, such genes are expressed precisely when the neighboring CGI is unmethylated but remain silenced otherwise...
February 21, 2017: Genome Research
https://www.readbyqxmd.com/read/28179366/genome-wide-chemical-mutagenesis-screens-allow-unbiased-saturation-of-the-cancer-genome-and-identification-of-drug-resistance-mutations
#19
Jonathan Brammeld, Mia Petljak, Inigo Martincorena, Steven P Williams, Luz Garcia Alonso, Alba Dalmases, Beatriz Bellosillo, Carla Daniela Robles-Espinoza, Stacey Price, Syd Barthorpe, Patrick Tarpey, Constantine Alifrangis, Graham Bignell, Joana Vidal, Jamie Young, Lucy Stebbings, Kathryn Beal, Michael R Stratton, Julio Saez-Rodriguez, Mathew Garnett, Clara Montagut, Francesco Iorio, Ultan McDermott
Drug resistance is an almost inevitable consequence of cancer therapy and ultimately proves fatal for the majority of patients. In many cases this is the consequence of specific gene mutations that have the potential to be targeted to re-sensitize the tumor. The ability to uniformly saturate the genome with point mutations without chromosome or nucleotide sequence context bias would open the door to identify all putative drug resistance mutations in cancer models. Here we describe such a method for elucidating drug resistance mechanisms using genome-wide chemical mutagenesis allied to next-generation sequencing...
February 8, 2017: Genome Research
https://www.readbyqxmd.com/read/28167665/microbial-strain-level-population-structure-and-genetic-diversity-from-metagenomes
#20
Duy Tin Truong, Adrian Tett, Edoardo Pasolli, Curtis Huttenhower, Nicola Segata
Among the human health conditions linked to microbial communities, phenotypes are often associated with only a subset of strains within causal microbial groups. While it has been critical for decades in microbial physiology to characterize individual strains, this has been challenging when using culture-independent high-throughput metagenomics. We introduce StrainPhlAn, a novel metagenomic strain identification approach, and apply it to characterize the genetic structure of thousands of strains from >125 species in >1,500 gut metagenomes drawn from populations spanning North/South American, European, Asian, and African countries...
February 6, 2017: Genome Research
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