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https://www.readbyqxmd.com/read/29786967/developmental-chromatin-restriction-of-pro-growth-gene-networks-acts-as-an-epigenetic-barrier-to-axon-regeneration-in-cortical-neurons
#1
Ishwariya Venkatesh, Vatsal Mehra, Zimei Wang, Ben Califf, Murray G Blackmore
Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age-dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome-wide maps of chromatin accessibility...
May 22, 2018: Developmental Neurobiology
https://www.readbyqxmd.com/read/29786918/novel-genes-and-insights-in-complete-asthma-remission
#2
Judith M Vonk, Maartje A E Nieuwenhuis, F Nicole Dijk, Anne Boudier, Valerie Siroux, Emmanuelle Bouzigon, Nicole Probst-Hensch, Medea Imboden, Dirk Keidel, Don Sin, Yohan Bossé, Ke Hao, Maarten van den Berge, Alen Faiz, Gerard H Koppelman, Dirkje S Postma
BACKGROUND: Asthma is a chronic respiratory disease without a cure, though there exists spontaneous remission. Genome wide association(GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. OBJECTIVES: We performed a GWA study to develop insights in asthma remission. METHODS: Clinical remission (ClinR) was defined by absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years, and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR)...
May 22, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29786687/genome-wide-analysis-of-circular-rnas-in-bovine-cumulus-cells-treated-with-bmp15-and-gdf9
#3
Yao Fu, Hao Jiang, Jian-Bo Liu, Xu-Lei Sun, Zhe Zhang, Sheng Li, Yan Gao, Bao Yuan, Jia-Bao Zhang
Circular RNAs (circRNAs) are important members of the non-coding RNA family, and those relating to animal physiologies have been widely studied in recent years. This study aimed to explore the roles of circRNAs in the regulation of follicular development. We constructed four bovine cumulus cell cDNA libraries, including a negative control group (NC) and groups treated with BMP15, GDF9 and BMP15 + GDF9, and we sequenced the libraries on the Illumina HiSeq Xten platform. We identified 1706 circRNAs and screened for differential circRNA expression...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29786556/assessment-of-stem-cell-differentiation-based-on-genome-wide-expression-profiles
#4
REVIEW
Patricio Godoy, Wolfgang Schmidt-Heck, Birte Hellwig, Patrick Nell, David Feuerborn, Jörg Rahnenführer, Kathrin Kattler, Jörn Walter, Nils Blüthgen, Jan G Hengstler
In recent years, protocols have been established to differentiate stem and precursor cells into more mature cell types. However, progress in this field has been hampered by difficulties to assess the differentiation status of stem cell-derived cells in an unbiased manner. Here, we present an analysis pipeline based on published data and methods to quantify the degree of differentiation and to identify transcriptional control factors explaining differences from the intended target cells or tissues. The pipeline requires RNA-Seq or gene array data of the stem cell starting population, derived 'mature' cells and primary target cells or tissue...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786095/high-throughput-creation-and-functional-profiling-of-dna-sequence-variant-libraries-using-crispr-cas9-in-yeast
#5
Xiaoge Guo, Alejandro Chavez, Angela Tung, Yingleong Chan, Christian Kaas, Yi Yin, Ryan Cecchi, Santiago Lopez Garnier, Eric D Kelsic, Max Schubert, James E DiCarlo, James J Collins, George M Church
Construction and characterization of large genetic variant libraries is essential for understanding genome function, but remains challenging. Here, we introduce a Cas9-based approach for generating pools of mutants with defined genetic alterations (deletions, substitutions, and insertions) with an efficiency of 80-100% in yeast, along with methods for tracking their fitness en masse. We demonstrate the utility of our approach by characterizing the DNA helicase SGS1 with small tiling deletion mutants that span the length of the protein and a series of point mutations against highly conserved residues in the protein...
May 21, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29786094/a-protein-activity-assay-to-measure-global-transcription-factor-activity-reveals-determinants-of-chromatin-accessibility
#6
Bei Wei, Arttu Jolma, Biswajyoti Sahu, Lukas M Orre, Fan Zhong, Fangjie Zhu, Teemu Kivioja, Inderpreet Sur, Janne Lehtiö, Minna Taipale, Jussi Taipale
No existing method to characterize transcription factor (TF) binding to DNA allows genome-wide measurement of all TF-binding activity in cells. Here we present a massively parallel protein activity assay, active TF identification (ATI), that measures the DNA-binding activity of all TFs in cell or tissue extracts. ATI is based on electrophoretic separation of protein-bound DNA sequences from a highly complex DNA library and subsequent mass-spectrometric identification of the DNA-bound proteins. We applied ATI to four mouse tissues and mouse embryonic stem cells and found that, in a given tissue or cell type, a small set of TFs, which bound to only ∼10 distinct motifs, displayed strong DNA-binding activity...
May 21, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29786076/c-myc-inhibits-myoblast-differentiation-and-promotes-myoblast-proliferation-and-muscle-fibre-hypertrophy-by-regulating-the-expression-of-its-target-genes-mirnas-and-lincrnas
#7
Wen Luo, Jiahui Chen, Limin Li, Xueyi Ren, Tian Cheng, Shiyi Lu, Raman Akinyanju Lawal, Qinghua Nie, Xiquan Zhang, Olivier Hanotte
The transcription factor c-Myc is an important regulator of cellular proliferation, differentiation and embryogenesis. While c-Myc can inhibit myoblast differentiation, the underlying mechanisms remain poorly understood. Here, we found that c-Myc does not only inhibits myoblast differentiation but also promotes myoblast proliferation and muscle fibre hypertrophy. By performing chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq), we identified the genome-wide binding profile of c-Myc in skeletal muscle cells...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785963/swi-snf-and-rsc-cooperate-to-reposition-and-evict-promoter-nucleosomes-at-highly-expressed-genes-in-yeast
#8
Yashpal Rawal, Răzvan V Chereji, Hongfang Qiu, Sudha Ananthakrishnan, Chhabi K Govind, David J Clark, Alan G Hinnebusch
The nucleosome remodeling complex RSC functions throughout the yeast genome to set the positions of -1 and +1 nucleosomes and thereby determines the widths of nucleosome-depleted regions (NDRs). The related complex SWI/SNF participates in nucleosome remodeling/eviction and promoter activation at certain yeast genes, including those activated by transcription factor Gcn4, but did not appear to function broadly in establishing NDRs. By analyzing the large cohort of Gcn4-induced genes in mutants lacking the catalytic subunits of SWI/SNF or RSC, we uncovered cooperation between these remodelers in evicting nucleosomes from different locations in the promoter and repositioning the +1 nucleosome downstream to produce wider NDRs-highly depleted of nucleosomes-during transcriptional activation...
May 21, 2018: Genes & Development
https://www.readbyqxmd.com/read/29785904/identification-of-an-immune-modulation-locus-utilising-a-bovine-mammary-gland-infection-challenge-model
#9
Mathew D Littlejohn, Sally-Anne Turner, Caroline G Walker, Sarah D Berry, Kathryn Tiplady, Ric G Sherlock, Greg Sutherland, Simon Swift, Dorian Garrick, S Jane Lacy-Hulbert, Scott McDougall, Richard J Spelman, Russell G Snell, J Eric Hillerton
Inflammation of the mammary gland following bacterial infection, commonly known as mastitis, affects all mammalian species. Although the aetiology and epidemiology of mastitis in the dairy cow are well described, the genetic factors mediating resistance to mammary gland infection are not well known, due in part to the difficulty in obtaining robust phenotypic information from sufficiently large numbers of individuals. To address this problem, an experimental mammary gland infection experiment was undertaken, using a Friesian-Jersey cross breed F2 herd...
May 2018: Journal of Dairy Research
https://www.readbyqxmd.com/read/29785501/improving-the-acetic-acid-tolerance-and-fermentation-of-acetobacter-pasteurianus-by-nucleotide-excision-repair-protein-uvra
#10
Yu Zheng, Jing Wang, Xiaolei Bai, Yangang Chang, Jun Mou, Jia Song, Min Wang
Acetic acid bacteria (AAB) are widely used in acetic acid fermentation due to their remarkable ability to oxidize ethanol and high tolerance against acetic acid. In Acetobacter pasteurianus, nucleotide excision repair protein UvrA was up-regulated 2.1 times by acetic acid when compared with that without acetic acid. To study the effects of UvrA on A. pasteurianus acetic acid tolerance, uvrA knockout strain AC2005-ΔuvrA, uvrA overexpression strain AC2005 (pMV24-uvrA), and the control strain AC2005 (pMV24), were constructed...
May 21, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29785398/marker-assisted-introgression-of-saltol-qtl-enhances-seedling-stage-salt-tolerance-in-the-rice-variety-pusa-basmati-1
#11
Vivek Kumar Singh, Brahma Deo Singh, Amit Kumar, Sadhna Maurya, Subbaiyan Gopala Krishnan, Kunnummal Kurungara Vinod, Madan Pal Singh, Ranjith Kumar Ellur, Prolay Kumar Bhowmick, Ashok Kumar Singh
Marker-assisted selection is an unequivocal translational research tool for crop improvement in the genomics era. Pusa Basmati 1 (PB1) is an elite Indian Basmati rice cultivar sensitive to salinity. Here, we report enhanced seedling stage salt tolerance in improved PB1 genotypes developed through marker-assisted transfer of a major QTL, Saltol . A highly salt tolerant line, FL478, was used as the Saltol donor. Parental polymorphism survey using 456 microsatellite (SSR)/QTL-linked markers revealed 14.3% polymorphism between PB1 and FL478...
2018: International Journal of Genomics
https://www.readbyqxmd.com/read/29785056/genome-wide-mapping-reveals-that-deoxyuridine-is-enriched-in-the-human-centromeric-dna
#12
Xiaoting Shu, Menghao Liu, Zhike Lu, Chenxu Zhu, Haowei Meng, Sihao Huang, Xiaoxue Zhang, Chengqi Yi
Uracil in DNA can be generated by cytosine deamination or dUMP misincorporation; however, its distribution in the human genome is poorly understood. Here we present a selective labeling and pull-down technology for genome-wide uracil profiling and identify thousands of uracil peaks in three different human cell lines. Surprisingly, uracil is highly enriched at the centromere of the human genome. Using mass spectrometry, we demonstrate that human centromeric DNA contains a higher level of uracil. We also directly verify the presence of uracil within two centromeric uracil peaks on chromosomes 6 and 11...
May 21, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29785040/archetypal-transcriptional-blocks-underpin-yeast-gene-regulation-in-response-to-changes-in-growth-conditions
#13
David Talavera, Christopher J Kershaw, Joseph L Costello, Lydia M Castelli, William Rowe, Paul F G Sims, Mark P Ashe, Chris M Grant, Graham D Pavitt, Simon J Hubbard
The transcriptional responses of yeast cells to diverse stresses typically include gene activation and repression. Specific stress defense, citric acid cycle and oxidative phosphorylation genes are activated, whereas protein synthesis genes are coordinately repressed. This view was achieved from comparative transcriptomic experiments delineating sets of genes whose expression greatly changed with specific stresses. Less attention has been paid to the biological significance of 1) consistent, albeit modest, changes in RNA levels across multiple conditions, and 2) the global gene expression correlations observed when comparing numerous genome-wide studies...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29785036/a-novel-microrna-signature-predicts-survival-in-liver-hepatocellular-carcinoma-after-hepatectomy
#14
Qiang Fu, Fan Yang, Tengxiao Xiang, Guoli Huai, Xingxing Yang, Liang Wei, Hongji Yang, Shaoping Deng
Liver hepatocellular carcinoma (LIHC) is the most common type of primary liver cancer. In the current study, genome-wide miRNA-Seq and mRNA profiles in 318 LIHC patients derived from The Cancer Genome Atlas (TCGA) were analysed to identify miRNA-based signatures for LIHC prognosis with survival analysis and a semi-supervised principal components (SPC) method. A seven-miRNA signature was confirmed for overall survival (OS) prediction by comparing miRNA profiles in paired primary tumour and solid tumour normal tissues...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29785027/targeting-g-quadruplex-dna-as-cognitive-function-therapy-for-atr-x-syndrome
#15
Norifumi Shioda, Yasushi Yabuki, Kouya Yamaguchi, Misaki Onozato, Yue Li, Kenji Kurosawa, Hideyuki Tanabe, Nobuhiko Okamoto, Takumi Era, Hiroshi Sugiyama, Takahito Wada, Kohji Fukunaga
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that Atrx mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted Xlr3b gene, regulating its expression by recruiting DNA methyltransferases...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29785011/a-genome-wide-cross-trait-analysis-from-uk-biobank-highlights-the-shared-genetic-architecture-of-asthma-and-allergic-diseases
#16
Zhaozhong Zhu, Phil H Lee, Mark D Chaffin, Wonil Chung, Po-Ru Loh, Quan Lu, David C Christiani, Liming Liang
Clinical and epidemiological data suggest that asthma and allergic diseases are associated and may share a common genetic etiology. We analyzed genome-wide SNP data for asthma and allergic diseases in 33,593 cases and 76,768 controls of European ancestry from UK Biobank. Two publicly available independent genome-wide association studies were used for replication. We have found a strong genome-wide genetic correlation between asthma and allergic diseases (rg  = 0.75, P = 6.84 × 10-62 ). Cross-trait analysis identified 38 genome-wide significant loci, including 7 novel shared loci...
May 21, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29785010/genome-wide-analyses-identify-68-new-loci-associated-with-intraocular-pressure-and-improve-risk-prediction-for-primary-open-angle-glaucoma
#17
Anthony P Khawaja, Jessica N Cooke Bailey, Nicholas J Wareham, Robert A Scott, Mark Simcoe, Robert P Igo, Yeunjoo E Song, Robert Wojciechowski, Ching-Yu Cheng, Peng T Khaw, Louis R Pasquale, Jonathan L Haines, Paul J Foster, Janey L Wiggs, Chris J Hammond, Pirro G Hysi
Glaucoma is the leading cause of irreversible blindness globally 1 . Despite its gravity, the disease is frequently undiagnosed in the community 2 . Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4 . Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP...
May 21, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29784972/comprehensive-analysis-of-the-mouse-cytochrome-p450-family-responsible-for-omega-3-epoxidation-of-eicosapentaenoic-acid
#18
Yosuke Isobe, Mai Itagaki, Yuko Ito, Satoko Naoe, Kotoe Kojima, Mitsunori Ikeguchi, Makoto Arita
Metabolites generated via oxygenation of the omega-3 double bond (omega-3 oxygenation) in eicosapentaenoic acid (EPA) have recently been identified as novel anti-inflammatory lipid mediators. Therefore, oxygenase(s) responsible for this metabolic pathway are of particular interest. We performed genome-wide screening of mouse cytochrome P450 (CYP) isoforms to explore enzymes involved in omega-3 oxygenation of EPA. As a result, 5 CYP isoforms (mouse Cyp1a2, 2c50, 4a12a, 4a12b, and 4f18) were selected and identified to confer omega-3 epoxidation of EPA to yield 17,18-epoxyeicosatetraenoic acid (17,18-EpETE)...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784950/genome-wide-association-study-identified-new-susceptible-genetic-variants-in-hla-class-i-region-for-hepatitis-b-virus-related-hepatocellular-carcinoma
#19
Hiromi Sawai, Nao Nishida, Seik-Soon Khor, Masao Honda, Masaya Sugiyama, Natsumi Baba, Kayoko Yamada, Norie Sawada, Shoichiro Tsugane, Kazuhiko Koike, Yuji Kondo, Hiroshi Yatsuhashi, Shinya Nagaoka, Akinobu Taketomi, Moto Fukai, Masayuki Kurosaki, Namiki Izumi, Jong-Hon Kang, Kazumoto Murata, Keisuke Hino, Sohji Nishina, Akihiro Matsumoto, Eiji Tanaka, Naoya Sakamoto, Koji Ogawa, Kazuhide Yamamoto, Akihiro Tamori, Osamu Yokosuka, Tatsuo Kanda, Isao Sakaida, Yoshito Itoh, Yuichiro Eguchi, Satoshi Oeda, Satoshi Mochida, Man-Fung Yuen, Wai-Kay Seto, Yong Poovorawan, Nawarat Posuwan, Masashi Mizokami, Katsushi Tokunaga
We have performed a genome-wide association study (GWAS) including 473 Japanese HBV (hepatitis B virus)-positive HCC (hepatocellular carcinoma) patients and 516 HBV carriers including chronic hepatitis and asymptomatic carrier individuals to identify new host genetic factors associated with HBV-derived HCC in Japanese and other East Asian populations. We identified 65 SNPs with P values < 10-4 located within the HLA class I region and three SNPs were genotyped in three independent population-based replication sets...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784899/pathway-based-analysis-of-genome-wide-association-study-of-circadian-phenotypes
#20
Di-di Zhu, Jia-Min Yuan, Rui Zhu, Yao Wang, Zhi-Yong Qian, Jian-Gang Zou
Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms (SNPs) which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies (GWAS) dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters...
November 1, 2017: Journal of Biomedical Research
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