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RNA epigenetic

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https://www.readbyqxmd.com/read/28225755/intragenic-dna-methylation-prevents-spurious-transcription-initiation
#1
Francesco Neri, Stefania Rapelli, Anna Krepelova, Danny Incarnato, Caterina Parlato, Giulia Basile, Mara Maldotti, Francesca Anselmi, Salvatore Oliviero
In mammals, DNA methylation occurs mainly at CpG dinucleotides. Methylation of the promoter suppresses gene expression, but the functional role of gene-body DNA methylation in highly expressed genes has yet to be clarified. Here we show that, in mouse embryonic stem cells, Dnmt3b-dependent intragenic DNA methylation protects the gene body from spurious RNA polymerase II entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that this Dnmt3b function is dependent on its enzymatic activity and recruitment to the gene body by H3K36me3...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28225006/altered-enhancer-transcription-underlies-huntington-s-disease-striatal-transcriptional-signature
#2
Stéphanie Le Gras, Céline Keime, Anne Anthony, Caroline Lotz, Lucie De Longprez, Emmanuel Brouillet, Jean-Christophe Cassel, Anne-Laurence Boutillier, Karine Merienne
Epigenetic and transcriptional alterations are both implicated in Huntington's disease (HD), a progressive neurodegenerative disease resulting in degeneration of striatal neurons in the brain. However, how impaired epigenetic regulation leads to transcriptional dysregulation in HD is unclear. Here, we investigated enhancer RNAs (eRNAs), a class of long non-coding RNAs transcribed from active enhancers. We found that eRNAs are expressed from many enhancers of mouse striatum and showed that a subset of those eRNAs are deregulated in HD vs control mouse striatum...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223461/identification-of-a-pseudomonas-aeruginosa-pao1-dna-methyltransferase-its-targets-and-physiological-roles
#3
Sebastian Doberenz, Denitsa Eckweiler, Olga Reichert, Vanessa Jensen, Boyke Bunk, Cathrin Spröer, Adrian Kordes, Emanuela Frangipani, Khai Luong, Jonas Korlach, Stephan Heeb, Jörg Overmann, Volkhard Kaever, Susanne Häussler
DNA methylation is widespread among prokaryotes, and most DNA methylation reactions are catalyzed by adenine DNA methyltransferases, which are part of restriction-modification (R-M) systems. R-M systems are known for their role in the defense against foreign DNA; however, DNA methyltransferases also play functional roles in gene regulation. In this study, we used single-molecule real-time (SMRT) sequencing to uncover the genome-wide DNA methylation pattern in the opportunistic pathogen Pseudomonas aeruginosa PAO1...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28219807/setd2-is-associated-with-strontium-induced-bone-regeneration
#4
Jia Xiaoshi, Long Qiaoyun, Richard J Miron, Yin Chengcheng, Wei Yan, Zhang Yufeng, Wu Min
: Strontium Ranelate has been utilized as a preventative treatment option for osteoporosis with the release of Sr ions having a direct effect on preventing osteoclast activation and promoting osteoblast differentiation. Previously our group has prepared and characterized a porous Sr-mesoporous bioactive glass (Sr-MBG) scaffold demonstrating its ability to enhance new bone formation when compared to MBG alone. The goal of the present study was to elucidate the bone-inducing properties of Sr by utilizing RNA-seq on in vivo tissue samples to investigate potential target genes responsible for Sr-induced new bone formation...
February 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28219335/stress-responsive-pathways-and-small-rna-changes-distinguish-variable-developmental-phenotypes-caused-by-msh1-loss
#5
Mon-Ray Shao, Sunil Kumar Kenchanmane Raju, John D Laurie, Robersy Sanchez, Sally A Mackenzie
BACKGROUND: Proper regulation of nuclear-encoded, organelle-targeted genes is crucial for plastid and mitochondrial function. Among these genes, MutS Homolog 1 (MSH1) is notable for generating an assortment of mutant phenotypes with varying degrees of penetrance and pleiotropy. Stronger phenotypes have been connected to stress tolerance and epigenetic changes, and in Arabidopsis T-DNA mutants, two generations of homozygosity with the msh1 insertion are required before severe phenotypes begin to emerge...
February 20, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28219123/identification-of-core-gene-networks-and-hub-genes-associated-with-progression-of-nonalcoholic-fatty-liver-disease-by-rna-sequencing
#6
Kikuko Hotta, Masataka Kikuchi, Takuya Kitamoto, Aya Kitamoto, Yuji Ogawa, Yasushi Honda, Takaomi Kessoku, Kaori Kobayashi, Masato Yoneda, Kento Imajo, Wataru Tomeno, Akihiro Nakaya, Yutaka Suzuki, Satoru Saito, Atsushi Nakajima
AIM: Nonalcoholic fatty liver disease (NAFLD) progresses because of the interaction between numerous genes. Thus, we performed weighted gene co-expression network analysis to identify core gene networks and key genes associated with NAFLD progression. METHODS: We enrolled 39 patients with mild NAFLD (fibrosis stages 0 to 2) and 21 with advanced NAFLD (fibrosis stages 3 or 4). Total RNA was extracted from frozen liver biopsies, and sequenced to capture a large dynamic range of expression levels...
February 20, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28218746/early-transcriptional-and-epigenetic-regulation-of-cd8-t-cell-differentiation-revealed-by-single-cell-rna-sequencing
#7
Boyko Kakaradov, Janilyn Arsenio, Christella E Widjaja, Zhaoren He, Stefan Aigner, Patrick J Metz, Bingfei Yu, Ellen J Wehrens, Justine Lopez, Stephanie H Kim, Elina I Zuniga, Ananda W Goldrath, John T Chang, Gene W Yeo
During microbial infection, responding CD8(+) T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA-sequencing approach and analyzed individual CD8(+) T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants that controlled the fate specification of CD8(+) T lymphocytes...
February 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28216634/detecting-rna-modifications-in-the-epitranscriptome-predict-and-validate
#8
REVIEW
Mark Helm, Yuri Motorin
RNA modifications are emerging players in the field of post-transcriptional regulation of gene expression, and are attracting a comparable degree of research interest to DNA and histone modifications in the field of epigenetics. We now know of more than 150 RNA modifications and the true potential of a few of these is currently emerging as the consequence of a leap in detection technology, principally associated with high-throughput sequencing. This Review outlines the major developments in this field through a structured discussion of detection principles, lays out advantages and drawbacks of new high-throughput methods and presents conventional biophysical identification of modifications as meaningful ways for validation...
February 20, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28215221/targeting-chromatin-remodeling-in-inflammation-and-fibrosis
#9
J Yang, B Tian, A R Brasier
Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28213474/a-bayesian-approach-for-analysis-of-whole-genome-bisulphite-sequencing-data-identifies-disease-associated-changes-in-dna-methylation
#10
Owen J L Rackham, Sarah R Langley, Thomas Oates, Eleni Vradi, Nathan Harmston, Prashant K Srivastava, Jacques Behmoaras, Petros Dellaportas, Leonardo Bottolo, Enrico Petretto
DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulphite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome whilst taking into account the distance between CpG sites as a covariate...
February 17, 2017: Genetics
https://www.readbyqxmd.com/read/28213279/tethering-rna-to-chromatin-for-fluorescence-microscopy-based-analysis-of-nuclear-organization
#11
Teresa Pankert, Thibaud Jegou, Maïwen Caudron-Herger, Karsten Rippe
Nuclear RNAs emerge as important factors to orchestrate the dynamic organization of the nucleus into functional subcompartments. By tethering RNAs to distinct genomic loci, the RNA-dependent chromatin changes can be dissected by fluorescence microscopic analysis. Here we describe how this approach is implemented in mammalian cells. It involves two high-affinity protein-nucleic acid interactions that can established with number of different protein domains and DNA and RNA sequences. A prototypic system is described here in detail: It consists of the binding of MS2 bacteriophage coat protein to its RNA recognition sequence and the interaction between the bacterial LacI repressor protein to its target lacO operator DNA sequences...
February 14, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28212444/sumo-modification-of-a-heterochromatin-histone-demethylase-jmjd2a-enables-viral-gene-transactivation-and-viral-replication
#12
Wan-Shan Yang, Mel Campbell, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification of chromatin has profound effects on transcription regulation. By using Kaposi's sarcoma associated herpesvirus (KSHV) as a model, we recently demonstrated that epigenetic modification of viral chromatin by SUMO-2/3 is involved in regulating gene expression and viral reactivation. However, how this modification orchestrates transcription reprogramming through targeting histone modifying enzymes remains largely unknown. Here we show that JMJD2A, the first identified Jumonji C domain-containing histone demethylase, is the histone demethylase responsible for SUMO-2/3 enrichment on the KSHV genome during viral reactivation...
February 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28212420/transcriptome-using-illumina-sequencing-reveals-the-traits-of-spermatogenesis-and-developing-testes-in-eriocheir-sinensis
#13
Gen-Liang Li, Hui Qian
Chinese mitten crab (Eriocheir sinensis) has the spermatozoa with typical aflagellate, decondensed chromatin, cup-shaped nuclei, and radial arms. However, the mechanism of spermatogenesis during which the specific spermatozoa are generated in this species is yet unclear. Here, the transcriptome of developing testis in E. sinensis was analyzed using the ways of RNA-seq and bioinformatics analysis to identify candidate genes potentially involved in development of testis and spermatogenesis. The Illumina HiSeq2500 sequencing of three replicons of samples produced a total of 145...
2017: PloS One
https://www.readbyqxmd.com/read/28212305/epigenetic-landscape-during-coronavirus-infection
#14
Alexandra Schäfer, Ralph S Baric
Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus-host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype...
February 15, 2017: Pathogens
https://www.readbyqxmd.com/read/28211524/epigenetic-and-genetic-dissections-of-uv-induced-global-gene-dysregulation-in-skin-cells-through-multi-omics-analyses
#15
Yao Shen, Milda Stanislauskas, Gen Li, Deyou Zheng, Liang Liu
To elucidate the complex molecular mechanisms underlying the adverse effects UV radiation (UVR) on skin homeostasis, we performed multi-omics studies to characterize UV-induced genetic and epigenetic changes. Human keratinocytes from a single donor treated with or without UVR were analyzed by RNA-seq, exome-seq, and H3K27ac ChIP-seq at 4 h and 72 h following UVR. Compared to the relatively moderate mutagenic effects of UVR, acute UV exposure induced substantial epigenomic and transcriptomic alterations, illuminating a previously underappreciated role of epigenomic and transcriptomic instability in skin pathogenesis...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209718/demethylation-of-h3k27-is-essential-for-the-induction-of-direct-cardiac-reprogramming-by-mir-combo
#16
Sophie Dal-Pra, Conrad P Hodgkinson, Maria Mirotsou, Imke Kirste, Victor J Dzau
Rationale: Direct reprogramming of cardiac fibroblasts to cardac omyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo using a combination of four microRNAs (miR-1, miR-133, miR-208 and miR-499) that we named miR combo. However, the mechanism of miR combo mediated direct cardiac reprogramming is currently unknown. Objective: Here we investigated the possibility that miR combo initiated direct cardiac reprogramming through an epigenetic mechanism...
February 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28209170/lincrnafezf1-as1-represses-p21-expression-to-promote-gastric-cancer-proliferation-through-lsd1-mediated-h3k4me2-demethylation
#17
Yan-Wen Liu, Rui Xia, Kai Lu, Min Xie, Fen Yang, Ming Sun, Wei De, Cailian Wang, Guozhong Ji
BACKGROUND: Although the prognosis of gastric cancer patients have a favorable progression, there are some patients with unusual patterns of locoregional and systemic recurrence. Therefore, a better understanding of early molecular events of the disease is needed. Current evidences demonstrate that long noncoding RNAs (lncRNAs) may be an important class of functional regulators involved in human gastric cancers development. Our previous studies suggest that HOTAIR contributes to gastric cancer development, and the overexpression of HOTAIR predicts a poor prognosis...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28206970/genetic-variation-in-long-noncoding-rnas-and-the-risk-of-nonalcoholic-fatty-liver-disease
#18
Silvia Sookoian, Cristian Rohr, Adrián Salatino, Hernán Dopazo, Tomas Fernandez Gianotti, Gustavo O Castaño, Carlos J Pirola
: The human transcriptome comprises a myriad of non protein-coding RNA species, including long noncoding RNAs (lncRNAs), which have a remarkable role in transcriptional and epigenetic regulation. We hypothesized that variants in lncRNAs influence the susceptibility to nonalcoholic fatty liver disease (NAFLD). Using next generation sequencing, we performed a survey of genetic variation associated with randomly selected lncRNA-genomic regions located within both experimentally validated and computationally predicted regulatory elements...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28203683/identification-of-unique-venous-thromboembolism-susceptibility-variants-in-african-americans
#19
John A Heit, Sebastian M Armasu, Bryan M McCauley, Iftikhar J Kullo, Hugues Sicotte, Jyotishman Pathak, Christopher G Chute, Omri Gottesman, Erwin P Bottinger, Joshua C Denny, Dan M Roden, Rongling Li, Marylyn D Ritchie, Mariza de Andrade
To identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype...
February 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28202544/cdc15-phosphorylates-carboxy-terminal-domain-of-rna-polymerase-ii-for-transcription-during-mitosis
#20
Amit Kumar Singh, Shivangi Rastogi, Harish Shukla, Mohd Asalam, Srikanta Kumar Rath, Md Sohail Akhtar
In eukaryotes, the basal transcription in interphase is orchestrated through the regulation by kinases (Kin28, Bur1 and Ctk1) and phosphatases (Ssu72, Rtr1 and Fcp1) which act through the post-translational modification of CTD (carboxy terminal domain of the largest subunit of RNA Polymerase II). The CTD comprises of repeated Tyr1Ser2Pro3Thr4Ser5Pro6Ser7 motif with potential epigenetic modification sites. Despite the observation of transcription and periodic expression of genes during mitosis with entailing CTD phosphorylation and dephosphorylation, the associated CTD specific kinase/s and its role in transcription remains unknown...
February 15, 2017: Journal of Biological Chemistry
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