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Genome Research

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https://www.readbyqxmd.com/read/30232199/metagenomic-analysis-with-strain-level-resolution-reveals-fine-scale-variation-in-the-human-pregnancy-microbiome
#1
Daniela S Aliaga Goltsman, Christine L Sun, Diana M Proctor, Daniel B DiGiulio, Anna Robaczewska, Brian C Thomas, Gary M Shaw, David K Stevenson, Susan P Holmes, Jillian F Banfield, David A Relman
Recent studies suggest that the microbiome has an impact on gestational health and outcome. However, characterization of the pregnancy-associated microbiome has largely relied on 16S rRNA gene amplicon-based surveys. Here, we describe an assembly-driven, metagenomics-based, longitudinal study of the vaginal, gut, and oral microbiomes in 292 samples from 10 subjects sampled every three weeks throughout pregnancy. Nonhuman sequences in the amount of 1.53 Gb were assembled into scaffolds, and functional genes were predicted for gene- and pathway-based analyses...
September 19, 2018: Genome Research
https://www.readbyqxmd.com/read/30232198/young-genes-have-distinct-gene-structure-epigenetic-profiles-and-transcriptional-regulation
#2
Michael S Werner, Bogdan Sieriebriennikov, Neel Prabh, Tobias Loschko, Christa Lanz, Ralf J Sommer
Species-specific, new, or 'orphan' genes account for 10-30% of eukaryotic genomes. Although initially considered to be of limited function, an increasing number of orphan genes have been shown to provide important phenotypic innovation. How new genes acquire regulatory sequences for proper temporal and spatial expression is unknown. Orphan gene regulation may rely in part on origination in open chromatin adjacent to pre-existing promoters, although this has not yet been assessed by genome-wide analysis of chromatin states...
September 19, 2018: Genome Research
https://www.readbyqxmd.com/read/30232197/deep-taxon-sampling-reveals-the-evolutionary-dynamics-of-novel-gene-families-in-%C3%A2-pristionchus-nematodes
#3
Neel Prabh, Waltraud Roeseler, Hanh Witte, Gabi Eberhardt, Ralf J Sommer, Christian Rödelsperger
The widespread identification of genes without detectable homology in related taxa is a hallmark of genome sequencing projects in animals, together with the abundance of gene duplications. Such genes have been called novel, young, taxon-restricted, or orphans, but little is known about the mechanisms accounting for their origin, age, and mode of evolution. Phylogenomic studies relying on deep and systematic taxon sampling and employing the comparative method can provide insight into the evolutionary dynamics acting on novel genes...
September 19, 2018: Genome Research
https://www.readbyqxmd.com/read/30232196/targeted-genome-fragmentation-with-crispr-cas9-enables-fast-and-efficient-enrichment-of-small-genomic-regions-and-ultra-accurate-sequencing-with-low-dna-input-crispr-ds
#4
Daniela Nachmanson, Shenyi Lian, Elizabeth K Schmidt, Michael J Hipp, Kathryn T Baker, Yuezheng Zhang, Maria Tretiakova, Kaitlyn Loubet-Senear, Brendan F Kohrn, Jesse J Salk, Scott R Kennedy, Rosa Ana Risques
Next-generation sequencing methods suffer from low recovery, uneven coverage, and false mutations. DNA fragmentation by sonication is a major contributor to these problems because it produces randomly sized fragments, PCR amplification bias, and end artifacts. In addition, oligonucleotide-based hybridization capture, a common target enrichment method, has limited efficiency for small genomic regions, contributing to low recovery. This becomes a critical problem in clinical applications, which value cost-effective approaches focused on the sequencing of small gene panels...
September 19, 2018: Genome Research
https://www.readbyqxmd.com/read/30228200/transcriptional-fates-of-human-specific-segmental-duplications-in-brain
#5
Max L Dougherty, Jason G Underwood, Bradley J Nelson, Elizabeth Tseng, Katherine M Munson, Osnat Penn, Tomasz J Nowakowski, Alex A Pollen, Evan E Eichler
Despite the importance of duplicate genes for evolutionary adaptation, accurate gene annotation is often incomplete, incorrect, or lacking in regions of segmental duplication. We developed an approach combining long-read sequencing and hybridization capture to yield full-length transcript information and confidently distinguish between nearly identical genes/paralogs. We used biotinylated probes to enrich for full-length cDNA from duplicated regions, which were then amplified, size-fractionated, and sequenced using single-molecule, long-read sequencing technology, permitting us to distinguish between highly identical genes by virtue of multiple paralogous sequence variants...
September 18, 2018: Genome Research
https://www.readbyqxmd.com/read/30228199/crosstalk-between-alternative-polyadenylation-and-mirna-in-regulation-of-protein-translational-efficiency
#6
Yonggui Fu, Liutao Chen, Chengyong Chen, Yutong Ge, Mingjing Kang, Zili Song, Jingwen Li, Yuchao Feng, Zhanfeng Huo, Guopei He, Mengmeng Hou, Shangwu Chen, Anlong Xu
3'UTRs play important roles in the gene regulation network via their influence on mRNA stability, translational efficiency and subcellular localization. For a given gene, 3'UTRs of different lengths generated by alternative polyadenylation (APA) may result in functional differences in regulation. The mechanistic details of how length changes of 3'UTRs alter gene function remains unclear. By combining APA sequencing and polysome profiling, we observed that mRNA isoforms with shorter 3'UTRs were bound with more polysomes in six cell lines but not in NIH3T3 cells, suggesting that changing 3'UTRs to shorter isoforms may lead to a higher gene translational efficiency...
September 18, 2018: Genome Research
https://www.readbyqxmd.com/read/30194096/gene-regulation-underlies-environmental-adaptation-in-house-mice
#7
Katya L Mack, Mallory A Ballinger, Megan Phifer-Rixey, Michael W Nachman
Changes in cis -regulatory regions are thought to play a major role in the genetic basis of adaptation. However, few studies have linked cis -regulatory variation with adaptation in natural populations. Here, using a combination of exome and RNA-seq data, we performed expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses to study the genetic architecture of regulatory variation in wild house mice ( Mus musculus domesticus ) using individuals from five populations collected along a latitudinal cline in eastern North America...
September 7, 2018: Genome Research
https://www.readbyqxmd.com/read/30171019/pioneering-chromatin-remodeling-and-epigenetic-constraint-in-early-t-cell-gene-regulation-by-spi1-pu-1
#8
Jonas Ungerbäck, Hiroyuki Hosokawa, Xun Wang, Tobias Strid, Brian A Williams, Mikael Sigvardsson, Ellen V Rothenberg
SPI1 (also known as PU.1) is a dominant but transient regulator in early T-cell precursors and a potent transcriptional controller of developmentally important pro-T-cell genes. Before T-lineage commitment, open chromatin is frequently occupied by PU.1, and many PU.1 sites lose accessibility when PU.1 is later down-regulated. Pioneering activity of PU.1 was tested in this developmentally dynamic context by quantitating the relationships between PU.1 occupancy and site quality and accessibility as PU.1 levels naturally declined in pro-T-cell development and by using stage-specific gain- and loss-of-function perturbations to relate binding to effects on target genes...
August 31, 2018: Genome Research
https://www.readbyqxmd.com/read/30166407/co-regulation-of-ribosomal-rna-with-hundreds-of-genes-contributes-to-phenotypic-variations
#9
Bo Li, Karl Kremling, Penghao Wu, Robert Bukowski, Maria Romay, En Xie, Edward Buckler, Mingsheng Chen
Ribosomal repeats occupy 5% of a plant genome, yet there has been little study of their diversity in the modern age of genomics. Ribosomal copy number and expression variations present an opportunity to tap a novel source of diversity. In the present study, we estimated the ribosomal DNA copy (rDNA) number and ribosomal RNA (rRNA) expression for a population of maize inbred lines, and investigated the potential role of rDNA and rRNA dosage in regulating global gene expression. Extensive variations were found in both ribosomal DNA copy number and ribosomal RNA expression among maize inbred lines...
August 30, 2018: Genome Research
https://www.readbyqxmd.com/read/30166406/study-of-mitotic-chromatin-supports-a-model-of-bookmarking-by-histone-modifications-and-reveals-nucleosome-deposition-patterns
#10
Elisheva Javasky, Inbal Shamir, Shashi Gandhi, Shawn Egri, Oded Sandler, Scott B Rothbart, Noam Kaplan, Jacob D Jaffe, Alon Goren, Itamar Simon
Mitosis encompasses key molecular changes including chromatin condensation, nuclear envelope breakdown, and reduced transcription levels. Immediately after mitosis, the interphase chromatin structure is reestablished and transcription resumes. The reestablishment of the interphase chromatin is probably achieved by 'bookmarking' i.e., the retention of at least partial information during mitosis. To gain a deeper understanding of the contribution of histone modifications to the mitotic bookmarking process, we merged proteomics, immunofluorescence, and ChIP-seq approaches...
August 30, 2018: Genome Research
https://www.readbyqxmd.com/read/30158147/a-massively-parallel-reporter-assay-reveals-context-dependent-activity-of-homeodomain-binding-sites-in-vivo
#11
Andrew E O Hughes, Connie A Myers, Joseph C Corbo
Cone-rod homeobox (CRX) is a paired-like homeodomain transcription factor (TF) and a master regulator of photoreceptor development in vertebrates. The in vitro DNA binding preferences of CRX have been described in detail, but the degree to which in vitro binding affinity is correlated with in vivo enhancer activity is not known. In addition, paired-class homeodomain TFs can bind DNA cooperatively as both homodimers and heterodimers at inverted TAAT half-sites separated by 2 or 3 nucleotides. This dimeric configuration is thought to mediate target specificity, but whether monomeric and dimeric sites encode distinct levels of activity is not known...
August 29, 2018: Genome Research
https://www.readbyqxmd.com/read/30154223/single-cell-rna-sequencing-reveals-the-existence-of-na%C3%A3-ve-and-primed-pluripotency-in-pre-implantation-rhesus-monkey-embryos
#12
Denghui Liu, Xinyi Wang, Dajian He, Chunli Sun, Xiechao He, Lanzhen Yan, Yizhou Li, Jing-Dong J Han, Ping Zheng
Naïve pluripotency exists in epiblast cells of the mouse pre-implantation embryos. However, whether the naïve pluripotency is transient or non-existent in primate embryos remains unclear. Using RNA-seq in single blastomeres from 16-cell embryos through to hatched blastocysts of rhesus monkey, we constructed the lineage segregation roadmap in which the specification of trophectoderm, epiblast and primitive endoderm is initiated simultaneously at the early blastocyst stage. Importantly, we uncovered the existence of distinct pluripotent states in monkey pre-implantation embryos...
August 28, 2018: Genome Research
https://www.readbyqxmd.com/read/30154222/polycomb-repressive-complex-1-shapes-the-nucleosome-landscape-but-not-accessibility-at-target-genes
#13
Hamish W King, Nadezda A Fursova, Neil P Blackledge, Rob J Klose
Polycomb group (PcG) proteins are transcriptional repressors that play important roles regulating gene expression during animal development. In vitro experiments have shown that PcG protein complexes can compact chromatin to limit the activity of chromatin remodelling enzymes and access of the transcriptional machinery to DNA. In fitting with these ideas, gene promoters associated with PcG proteins have been reported to be less accessible than other gene promoters. However, it remains largely untested in vivo whether PcG proteins define chromatin accessibility or other chromatin features...
August 28, 2018: Genome Research
https://www.readbyqxmd.com/read/30143598/epigenetic-analyses-of-planarian-stem-cells-demonstrate-conservation-of-bivalent-histone-modifications-in-animal-stem-cells
#14
Anish Dattani, Damian Kao, Yuliana Mihaylova, Prasad Abnave, Samantha Hughes, Alvina Lai, Sounak Sahu, A Aziz Aboobaker
Planarian flatworms have an indefinite capacity to regenerate missing or damaged body parts owing to a population of pluripotent adult stems cells called neoblasts (NBs). Currently, little is known about the importance of the epigenetic status of NBs and how histone modifications regulate homeostasis and cellular differentiation. We have developed an improved and optimized ChIP-seq protocol for NBs in Schmidtea mediterranea and have generated genome-wide profiles for the active marks H3K4me3 and H3K36me3, and suppressive marks H3K4me1 and H3K27me3...
August 24, 2018: Genome Research
https://www.readbyqxmd.com/read/30143597/a-compendium-of-conserved-cleavage-and-polyadenylation-events-in-mammalian-genes
#15
Ruijia Wang, Dinghai Zheng, Ghassan Yehia, Bin Tian
Cleavage and polyadenylation is essential for 3' end processing of almost all eukaryotic mRNAs. Recent studies have shown widespread alternative cleavage and polyadenylation (APA) events leading to mRNA isoforms with different 3' UTRs and/or coding sequences. Here, we present a compendium of conserved cleavage and polyadenylation sites (PASs) in mammalian genes, based on approximately 1.2 billion 3' end sequencing reads from more than 360 human, mouse, and rat samples. We show that ∼80% of mammalian mRNA genes contain at least one conserved PAS, and ∼50% have conserved APA events...
August 24, 2018: Genome Research
https://www.readbyqxmd.com/read/30143596/exonic-splice-regulation-imposes-strong-selection-at-synonymous-sites
#16
Rosina Savisaar, Laurence D Hurst
What proportion of coding sequence nucleotides have roles in splicing, and how strong is the selection that maintains them? Despite a large body of research into exonic splice regulatory signals, these questions have not been answered. This is because, to our knowledge, previous investigations have not explicitly disentangled the frequency of splice regulatory elements from the strength of the evolutionary constraint under which they evolve. Current data are consistent both with a scenario of weak and diffuse constraint, enveloping large swaths of sequence, as well as with well-defined pockets of strong purifying selection...
August 24, 2018: Genome Research
https://www.readbyqxmd.com/read/30139769/human-cardiac-cis-regulatory-elements-their-cognate-transcription-factors-and-regulatory-dna-sequence-variants
#17
Dongwon Lee, Ashish Kapoor, Alexias Safi, Lingyun Song, Marc K Halushka, Gregory E Crawford, Aravinda Chakravarti
Cis -regulatory elements (CRE), short DNA sequences through which transcription factors (TFs) exert regulatory control on gene expression, are postulated to be the major sites of causal sequence variation underlying the genetics of complex traits and diseases. We present integrative analyses, combining high-throughput genomic and epigenomic data with sequence-based computations, to identify the causal transcriptional components in a given tissue. We use data on adult human hearts to demonstrate that (1) sequence-based predictions detect numerous, active, tissue-specific CREs missed by experimental observations, (2) learned sequence features identify the cognate TFs, (3) CRE variants are specifically associated with cardiac gene expression, and (4) a significant fraction of the heritability of exemplar cardiac traits (QT interval, blood pressure, pulse rate) is attributable to these variants...
August 23, 2018: Genome Research
https://www.readbyqxmd.com/read/30135090/phenotypically-distinct-female-castes-in-honey-bees-are-defined-by-alternative-chromatin-states-during-larval-development
#18
Marek Wojciechowski, Robert Lowe, Joanna Maleszka, Danyal Conn, Ryszard Maleszka, Paul J Hurd
The capacity of the honey bee to produce three phenotypically distinct organisms (two female castes; queens and sterile workers, and haploid male drones) from one genotype represents one of the most remarkable examples of developmental plasticity in any phylum. The queen-worker morphological and reproductive divide is environmentally controlled during post-embryonic development by differential feeding. Previous studies implicated metabolic flux acting via epigenetic regulation, in particular DNA methylation and microRNAs, in establishing distinct patterns of gene expression underlying caste-specific developmental trajectories...
August 22, 2018: Genome Research
https://www.readbyqxmd.com/read/30181341/corrigendum-large-scale-analysis-of-genome-and-transcriptome-alterations-in-multiple-tumors-unveils-novel-cancer-relevant-splicing-networks
#19
Endre Sebestyén, Babita Singh, Belén Miñana, Amadís Pagès, Francesca Mateo, Miguel Angel Pujana, Juan Valcárcel, Eduardo Eyras
No abstract text is available yet for this article.
September 2018: Genome Research
https://www.readbyqxmd.com/read/30108180/natural-genetic-variation-in-c-elegans-identified-genomic-loci-controlling-metabolite-levels
#20
Arwen W Gao, Mark G Sterken, Jelmi Uit de Bos, Jelle van Creij, Rashmi Kamble, Basten L Snoek, Jan E Kammenga, Riekelt H Houtkooper
Metabolic homeostasis is sustained by complex biological networks that respond to nutrient availability. Genetic and environmental factors may disrupt this equilibrium, leading to metabolic disorders, including obesity and type 2 diabetes. To identify the genetic factors controlling metabolism, we performed quantitative genetic analysis using a population of 199 recombinant inbred lines (RILs) in the nematode Caenorhabditis elegans We focused on the genomic regions that control metabolite levels by measuring fatty acid (FA) and amino acid (AA) composition in the RILs using targeted metabolomics...
September 2018: Genome Research
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