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https://www.readbyqxmd.com/read/28213474/a-bayesian-approach-for-analysis-of-whole-genome-bisulphite-sequencing-data-identifies-disease-associated-changes-in-dna-methylation
#1
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/28212305/epigenetic-landscape-during-coronavirus-infection
#2
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/28209718/demethylation-of-h3k27-is-essential-for-the-induction-of-direct-cardiac-reprogramming-by-mir-combo
#3
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/28208788/next-generation%C3%A2-sequencing-based%C3%A2-ribomethseq%C3%A2-protocol%C3%A2-for%C3%A2-analysis%C3%A2-of%C3%A2-trna%C3%A2-2-o-methylation
#4
Virginie Marchand, Florian Pichot, Kathrin Thüring, Lilia Ayadi, Isabel Freund, Alexander Dalpke, Mark Helm, Yuri Motorin
Analysis of RNA modifications by traditional physico-chemical approaches is labor  intensive,  requires  substantial  amounts  of  input  material  and  only  allows  site-by-site  measurements.  The  recent  development  of  qualitative  and  quantitative  approaches  based  on   next-generation sequencing (NGS) opens new perspectives for the analysis of various cellular RNA  species.  The  Illumina  sequencing-based  RiboMethSeq  protocol  was  initially  developed  and  successfully applied for mapping of ribosomal RNA (rRNA) 2'-O-methylations...
February 9, 2017: Biomolecules
https://www.readbyqxmd.com/read/28208729/altered-intracellular-milieu-of-adar2-deficient-motor-neurons-in-amyotrophic-lateral-sclerosis
#5
REVIEW
Takenari Yamashita, Megumi Akamatsu, Shin Kwak
Transactive response DNA-binding protein (TDP-43) pathology, and failure of A-to-I conversion (RNA editing) at the glutamine/arginine (Q/R) site of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of most patients with amyotrophic lateral sclerosis (ALS). Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes GluA2 Q/R site-RNA editing. Furthermore, conditional ADAR2 knockout mice (AR2) exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons, which is the most reliable pathological marker of ALS...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28208632/cross-talk-between-dnmt2-dependent-trna-methylation-and-queuosine-modification
#6
REVIEW
Ann E Ehrenhofer-Murray
Enzymes of the Dnmt2 family of methyltransferases have yielded a number of unexpected discoveries. The first surprise came more than ten years ago when it was realized that, rather than being DNA methyltransferases, Dnmt2 enzymes actually are transfer RNA (tRNA) methyltransferases for cytosine-5 methylation, foremost C38 (m5C38) of tRNAAsp. The second unanticipated finding was our recent discovery of a nutritional regulation of Dnmt2 in the fission yeast Schizosaccharomyces pombe. Significantly, the presence of the nucleotide queuosine in tRNAAsp strongly stimulates Dnmt2 activity both in vivo and in vitro in S...
February 10, 2017: Biomolecules
https://www.readbyqxmd.com/read/28208626/2-o-methyl-rna-ethylene-bridged-nucleic-acid-chimera-antisense-oligonucleotides-to-induce-dystrophin-exon-45-skipping
#7
REVIEW
Tomoko Lee, Hiroyuki Awano, Mariko Yagi, Masaaki Matsumoto, Nobuaki Watanabe, Ryoya Goda, Makoto Koizumi, Yasuhiro Takeshima, Masafumi Matsuo
Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease characterized by dystrophin deficiency from mutations in the dystrophin gene. Antisense oligonucleotide (AO)-mediated exon skipping targets restoration of the dystrophin reading frame to allow production of an internally deleted dystrophin protein with functional benefit for DMD patients who have out-of-frame deletions. After accelerated US approval of eteplirsen (Exondys 51), which targets dystrophin exon 51 for skipping, efforts are now focused on targeting other exons...
February 10, 2017: Genes
https://www.readbyqxmd.com/read/28205605/the-role-of-the-rna-demethylase-fto-fat-mass-and-obesity-associated-and-mrna-methylation-in-hippocampal-memory-formation
#8
Brandon J Walters, Valentina Mercaldo, Colleen J Gillon, Matthew Yip, Rachael L Neve, Frederick M Boyce, Paul W Frankland, Sheena A Josselyn
The formation of long-lasting memories requires coordinated changes in gene expression and protein synthesis (Davis and Squire, 1984; Duvarci et al, 2008; Hernandez and Abel, 2008). Although many studies implicate DNA modifications (DNA methylation, histone modifications) in memory formation, the contributions of RNA modifications remain largely unexplored. Here, we investigated the role of mRNA methylation in hippocampal-dependent memory formation in mice. RNA modifications are highly dynamic and readily reversible (Jia et al, 2013)...
February 16, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28205560/alkb-homolog-3-mediated-trna-demethylation-promotes-protein-synthesis-in-cancer-cells
#9
Yuko Ueda, Ikumi Ooshio, Yasuyuki Fusamae, Kaori Kitae, Megumi Kawaguchi, Kentaro Jingushi, Hiroaki Hase, Kazuo Harada, Kazumasa Hirata, Kazutake Tsujikawa
The mammalian AlkB homolog (ALKBH) family of proteins possess a 2-oxoglutarate- and Fe(II)-dependent oxygenase domain. A similar domain in the Escherichia coli AlkB protein catalyzes the oxidative demethylation of 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) in both DNA and RNA. AlkB homolog 3 (ALKBH3) was also shown to demethylate 1-meA and 3-meC (induced in single-stranded DNA and RNA by a methylating agent) to reverse the methylation damage and retain the integrity of the DNA/RNA. We previously reported the high expression of ALKBH3 in clinical tumor specimens and its involvement in tumor progression...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203244/pistil-transcriptome-analysis-to-disclose-genes-and-gene-products-related-to-aposporous-apomixis-in-hypericum-perforatum-l
#10
Giulio Galla, Sara Zenoni, Linda Avesani, Lothar Altschmied, Paride Rizzo, Timothy F Sharbel, Gianni Barcaccia
Unlike sexual reproduction, apomixis encompasses a number of reproductive strategies, which permit maternal genome inheritance without genetic recombination and syngamy. The key biological features of apomixis are the circumvention of meiosis (i.e., apomeiosis), the differentiation of unreduced embryo sacs and egg cells, and their autonomous development in functional embryos through parthenogenesis, and the formation of viable endosperm either via fertilization-independent means or following fertilization with a sperm cell...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28202376/structural-features-of-zika-virus-non-structural-proteins-3-and-5-and-its-individual-domains-in-solution-as-well-as-insights-into-ns3-inhibition
#11
Wuan Geok Saw, Ankita Pan, Malathy Sony Subramanian Manimekalai, Gerhard Grüber
Zika virus (ZIKV) has emerged as a pathogen of major health concern. The virus relies on its non-structural protein 5 (NS5) including a methyl-transferase (MTase) and a RNA-dependent RNA polymerase (RdRp) for capping and synthesis of the viral RNA and the nonstructural protein 3 (NS3) with its protease and helicase domain for polyprotein possessing, unwinding dsRNA proceeding replication, and NTPase/RTPase activities. In this study we present for the first time insights into the overall structure of the entire French Polynesia ZIKV NS3 in solution...
February 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28196088/transcriptomic-cellular-and-life-history-responses-of-daphnia-magna-chronically-exposed-to-benzotriazoles-endocrine-disrupting-potential-and-molting-effects
#12
Maeva Giraudo, Mélanie Douville, Guillaume Cottin, Magali Houde
Benzotriazoles (BZTs) are ubiquitous aquatic contaminants used in a wide range of industrial and domestic applications from aircraft deicers to dishwasher tablets. Acute toxicity has been reported in aquatic organisms for some of the BZTs but their mode of action remains unknown. The objectives of this study were to evaluate the transcriptomic response of D. magna exposed to sublethal doses of 1H-benzotriazole (BTR), 5-methyl-1H-benzotriazole (5MeBTR) and 5-chloro-1H-benzotriazole (5ClBTR) using RNA-sequencing and quantitative real-time PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28195308/ca-2-permeable-ampa-receptors-associated-with-epileptogenesis-of-hypothalamic-hamartoma
#13
Hiroki Kitaura, Masaki Sonoda, Sayaka Teramoto, Hiroshi Shirozu, Hiroshi Shimizu, Tadashi Kimura, Hiroshi Masuda, Yosuke Ito, Hitoshi Takahashi, Shin Kwak, Shigeki Kameyama, Akiyoshi Kakita
Hypothalamic hamartoma (HH), composed of neurons and glia without apparent cytologic abnormalities, is a rare developmental malformation in humans. Patients with HH often have characteristic medically refractory gelastic seizures, and intrinsic epileptogenesis within the lesions has been speculated. Herein we provide evidence to suggest that in HH neurons, Ca(2+) permeability through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors is aberrantly elevated. In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues...
February 13, 2017: Epilepsia
https://www.readbyqxmd.com/read/28194035/recurrently-deregulated-lncrnas-in-hepatocellular-carcinoma
#14
Yang Yang, Lei Chen, Jin Gu, Hanshuo Zhang, Jiapei Yuan, Qiuyu Lian, Guishuai Lv, Siqi Wang, Yang Wu, Yu-Cheng T Yang, Dongfang Wang, Yang Liu, Jing Tang, Guijuan Luo, Yang Li, Long Hu, Xinbao Sun, Dong Wang, Mingzhou Guo, Qiaoran Xi, Jianzhong Xi, Hongyang Wang, Michael Q Zhang, Zhi John Lu
Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193906/cbx3-promotes-colon-cancer-cell-proliferation-by-cdk6-kinase-independent-function-during-cell-cycle
#15
Yao Fan, Haiping Li, Xiaolong Liang, Zheng Xiang
Heterochromatin protein 1γ (CBX3) links histone methylation marks to transcriptional silence, DNA repair and RNA splicing, but a role for CBX3 in cancer remains largely unknown. In this study, we show that CBX3 in colon cancer cells promotes the progression of the cell cycle and proliferation in vitro and in vivo. Cell cycle (G1 phase to S phase) related gene CDK6 and p21 were further identified as targets of CBX3. In addition, we found that enhancing CDK6 suppresses cell proliferation by upregulating inhibitor p21 in the absence of CBX3, and this function is independent of the kinase activity of CDK6...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193737/exogenous-transposable-elements-circumvent-identity-based-silencing-permitting-the-dissection-of-expression-dependent-silencing
#16
Dalen Fultz, R Keith Slotkin
The propagation of epigenetic marks has received a great deal of attention, yet the initiation of epigenetic silencing of a new transgene, virus, or transposable element (TE) remains enigmatic. The overlapping and simultaneous function of multiple silencing mechanisms has obscured this area of investigation. Here, we have revealed two broad mechanisms that can initiate silencing independently: identity-based and expression-dependent silencing. We found that identity-based silencing is targeted by 21-22 or 24 nucleotide small interfering RNAs (siRNAs) generated from previously silenced regions of the genome...
February 13, 2017: Plant Cell
https://www.readbyqxmd.com/read/28192788/metabolic-gatekeeper-function-of-b-lymphoid-transcription-factors
#17
Lai N Chan, Zhengshan Chen, Daniel Braas, Jae-Woong Lee, Gang Xiao, Huimin Geng, Kadriye Nehir Cosgun, Christian Hurtz, Seyedmehdi Shojaee, Valeria Cazzaniga, Hilde Schjerven, Thomas Ernst, Andreas Hochhaus, Steven M Kornblau, Marina Konopleva, Miles A Pufall, Giovanni Cazzaniga, Grace J Liu, Thomas A Milne, H Phillip Koeffler, Theodora S Ross, Isidro Sánchez-García, Arndt Borkhardt, Keith R Yamamoto, Ross A Dickins, Thomas G Graeber, Markus Müschen
B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply...
February 13, 2017: Nature
https://www.readbyqxmd.com/read/28192787/m-6-a-dependent-maternal-mrna-clearance-facilitates-zebrafish-maternal-to-zygotic-transition
#18
Boxuan Simen Zhao, Xiao Wang, Alana V Beadell, Zhike Lu, Hailing Shi, Adam Kuuspalu, Robert K Ho, Chuan He
The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N(6)-methyladenosine (m(6)A) modified, and the clearance of these maternal mRNAs is facilitated by an m(6)A-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of m(6)A-modified maternal mRNAs and impedes zygotic genome activation...
February 13, 2017: Nature
https://www.readbyqxmd.com/read/28188267/phosphorylation-of-spt5-by-cdkd-2-is-required-for-vip5-recruitment-and-normal-flowering-in-arabidopsis-thaliana
#19
Chengyuan Lu, Yongke Tian, Shiliang Wang, Yanhua Su, Ting Mao, Tongtong Huang, Qingqing Chen, Zuntao Xu, Yong Ding
The elongation factor suppressor of Ty 5 homolog (Spt5) is a regulator of transcription and histone methylation. In humans, phosphorylation of SPT5 by P-TEFb, a protein kinase composed of Cyclin-dependent kinase 9 (CDK9) and cyclin T, interacts with the RNA polymerase II-associated factor1 (PAF1) complex. However, the mechanism of SPT5 phosphorylation is not well understood in plants. Here, we examine the function of SPT5 in Arabidopsis thaliana, and find that spt5 mutant flowers early under long-day and short-day conditions...
February 10, 2017: Plant Cell
https://www.readbyqxmd.com/read/28188229/the-human-long-interspersed-element-1-retrotransposon-an-emerging-biomarker-of-neoplasia
#20
REVIEW
Daniel Ardeljan, Martin S Taylor, David T Ting, Kathleen H Burns
BACKGROUND: A large portion of intronic and intergenic space in our genome consists of repeated sequences. One of the most prevalent is the long interspersed element-1 (LINE-1, L1) mobile DNA. LINE-1 is rightly receiving increasing interest as a cancer biomarker. CONTENT: Intact LINE-1 elements are self-propagating. They code for RNA and proteins that function to make more copies of the genomic element. Our current understanding is that this process is repressed in most normal cells, but that LINE-1 expression is a hallmark of many types of malignancy...
February 10, 2017: Clinical Chemistry
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