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Cytosine methylation

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https://www.readbyqxmd.com/read/29164502/superovulation-alters-dna-methyltransferase-protein-expression-in-mouse-oocytes-and-early-embryos
#1
Fatma Uysal, Saffet Ozturk, Gokhan Akkoyunlu
PURPOSE: DNA methylation is an epigenetic mechanism that plays critical roles during mammalian oocyte and preimplantation embryo development. It is achieved by adding a methyl group to the fifth carbon atom of cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites using DNA methyltransferase (DNMT) enzymes for de novo and maintenance methylation processes. DNMT1, DNMT3A, and DNMT3B play important roles in establishing methylation of developmentally related genes in oocytes and early embryos...
November 22, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29163634/evidence-suggesting-absence-of-mitochondrial-dna-methylation
#2
Mie Mechta, Lars R Ingerslev, Odile Fabre, Martin Picard, Romain Barrès
Methylation of nuclear genes encoding mitochondrial proteins participates in the regulation of mitochondria function. The existence of cytosine methylation in the mitochondrial genome is debated. To investigate whether mitochondrial DNA (mtDNA) is methylated, we used both targeted- and whole mitochondrial genome bisulfite sequencing in cell lines and muscle tissue from mouse and human origin. While unconverted cytosines were detected in some portion of the mitochondrial genome, their abundance was inversely associated to the sequencing depth, indicating that sequencing analysis can bias the estimation of mtDNA methylation levels...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29161430/methbank-3-0-a-database-of-dna-methylomes-across-a-variety-of-species
#3
Rujiao Li, Fang Liang, Mengwei Li, Dong Zou, Shixiang Sun, Yongbing Zhao, Wenming Zhao, Yiming Bao, Jingfa Xiao, Zhang Zhang
MethBank (http://bigd.big.ac.cn/methbank) is a database that integrates high-quality DNA methylomes across a variety of species and provides an interactive browser for visualization of methylation data. Here, we present an updated implementation of MethBank (version 3.0) by incorporating more DNA methylomes from multiple species and equipping with more enhanced functionalities for data annotation and more friendly web interfaces for data presentation, search and visualization. MethBank 3.0 features large-scale integration of high-quality methylomes, involving 34 consensus reference methylomes derived from a large number of human samples, 336 single-base resolution methylomes from different developmental stages and/or tissues of five plants, and 18 single-base resolution methylomes from gametes and early embryos at multiple stages of two animals...
November 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29159284/measuring-quantitative-effects-of-methylation-on-transcription-factor-dna-binding-affinity
#4
Zheng Zuo, Basab Roy, Yiming Kenny Chang, David Granas, Gary D Stormo
Methylation of CpG (cytosine-phosphate-guanine) dinucleotides is a common epigenetic mark that influences gene expression. The effects of methylation on transcription factor (TF) binding are unknown for most TFs and, even when known, such knowledge is often only qualitative. In reality, methylation sensitivity is a quantitative effect, just as changes to the DNA sequence have quantitative effects on TF binding affinity. We describe Methyl-Spec-seq, an easy-to-use method that measures the effects of CpG methylation (mCPG) on binding affinity for hundreds to thousands of variants in parallel, allowing one to quantitatively assess the effects at every position in a binding site...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-alpha-ketoglutarate-and-tet-tdg-functional-reactivation
#5
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Künne, Stefan Günther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sueruen, Frank Schnutgen, Harald von Melchner, Antonella Di Stilo, Manuela Aragno, Maarten Braspenning, Wim Van Criekinge, Miles J De Blasio, Rebecca H Ritchie, Germana Zaccagnini, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically-relevant primary cell population. Diabetes compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of α-ketoglutarate (αKG) in the epi-metabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs)...
November 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/29149287/genomic-and-epigenomic-immunity-in-common-bean-the-unusual-features-of-nb-lrr-gene-family
#6
Manon M S Richard, Ariane Gratias, Vincent Thareau, Kyung Do Kim, Sandrine Balzergue, Johann Joets, Scott A Jackson, Valérie Geffroy
In plants, a key class of genes comprising most of disease resistance (R) genes encodes Nucleotide-binding leucine-rich repeat (NL) proteins. Access to common bean (Phaseolus vulgaris) genome sequence provides unparalleled insight into the organization and evolution of this large gene family (∼400 NL) in this important crop. As observed in other plant species, most common bean NL are organized in cluster of genes. However, a particularity of common bean is that these clusters are often located in subtelomeric regions close to terminal knobs containing the satellite DNA khipu...
November 15, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29140247/ddm1-and-lsh-remodelers-allow-methylation-of-dna-wrapped-in-nucleosomes
#7
David B Lyons, Daniel Zilberman
Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29139326/dna-polymerase-%C3%AE-mutational-signatures-are-found-in-a-variety-of-different-types-of-cancer
#8
Igor B Rogozin, Alexander Goncearenco, Artem G Lada, Subhajyoti De, German Nudelman, Anna R Panchenko, David N Cooper, Youri I Pavlov
DNA polymerase (pol) η is a specialized error-prone polymerase with at least two quite different and contrasting cellular roles: to mitigate the genetic consequences of solar UV irradiation, and promote somatic hypermutation in the variable regions of immunoglobulin genes. Misregulation and mistargeting of pol η can compromise genome integrity. We explored whether the mutational signature of pol η could be found in datasets of human somatic mutations derived from normal and cancer cells. A substantial excess of single and tandem somatic mutations within known pol η mutable motifs was noted in skin cancer as well as in many other types of human cancer, suggesting that somatic mutations in A:T bases generated by DNA polymerase η are a common feature of tumorigenesis...
November 15, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29130343/defining-baseline-epigenetic-landscapes-in-the-rat-liver
#9
John P Thomson, Raffaele Ottaviano, Roland Buesen, Jonathan G Moggs, Michael Schwarz, Richard R Meehan
Characterization of the hepatic epigenome following exposure to chemicals and therapeutic drugs provides novel insights into toxicological and pharmacological mechanisms, however appreciation of genome-wide inter- and intra-strain baseline epigenetic variation, particularly in under-characterized species such as the rat is limited. Material & methods: To enhance the utility of epigenomic endpoints safety assessment, we map both DNA modifications (5-methyl-cytosine and 5-hydroxymethyl-cytosine) and enhancer related chromatin marks (H3K4me1 and H3K27ac) across multiple male and female rat livers for two important outbred laboratory rat strains (Sprague-Dawley and Wistar)...
November 13, 2017: Epigenomics
https://www.readbyqxmd.com/read/29118064/leukocyte-counts-based-on-dna-methylation-at-individual-cytosines
#10
Joana Frobel, Tanja Božić, Michael Lenz, Peter Uciechowski, Yang Han, Reinhild Herwartz, Klaus Strathmann, Susanne Isfort, Jens Panse, André Esser, Carina Birkhofer, Uwe Gerstenmaier, Thomas Kraus, Lothar Rink, Steffen Koschmieder, Wolfgang Wagner
BACKGROUND: White blood cell counts are routinely measured with automated hematology analyzers, by flow cytometry, or by manual counting. Here, we introduce an alternative approach based on DNA methylation (DNAm) at individual CG dinucleotides (CpGs). METHODS: We identified candidate CpGs that were nonmethylated in specific leukocyte subsets. DNAm levels (ranging from 0% to 100%) were analyzed by pyrosequencing and implemented into deconvolution algorithms to determine the relative composition of leukocytes...
November 8, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29106556/location-matters-distinct-dna-methylation-patterns-in-gabaergic-interneuronal-populations-from-separate-microcircuits-within-the-human-hippocampus
#11
W Brad Ruzicka, Sivan Subburaju, Joseph T Coyle, Francine M Benes
Recent studies describe distinct DNA methylomes among phenotypic subclasses of neurons in the human brain, but variation in DNA methylation between common neuronal phenotypes distinguished by their function within distinct neural circuits remains an unexplored concept. Studies able to resolve epigenetic profiles at the level of microcircuits are needed to illuminate chromatin dynamics in the regulation of specific neuronal populations and circuits mediating normal and abnormal behaviors.The Illumina HumanMethylation450 BeadChip was used to assess genome-wide DNA methylation in stratum oriens GABAergic interneurons sampled by laser-microdissection from two discrete microcircuits along the trisynaptic pathway in postmortem human hippocampus from eight control, eight schizophrenia, and eight bipolar disorder subjects...
November 2, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29105762/regulation-of-genome-wide-dna-methylation-by-mobile-small-rnas
#12
REVIEW
Muluneh Tamiru, Thomas J Hardcastle, Mathew G Lewsey
Contents I. II. III. IV. V. VI. VII. VIII. IX. References SUMMARY: RNA-directed DNA methylation (RdDM) at cytosine residues regulates gene expression, silences transposable elements and influences genome stability. The mechanisms responsible for RdDM are guided to target loci by small RNAs (sRNAs) that can move within plants cell to cell and long distance. Here we discuss recent advances in the understanding of interactions between mobile sRNAs and DNA methylation. We describe the mechanisms of sRNA movement, the differences between known classes of mobile sRNA-DNA methylation interactions and the limits of current knowledge...
November 6, 2017: New Phytologist
https://www.readbyqxmd.com/read/29103146/rna-cytosine-methyltransferase-nsun3-regulates-embryonic-stem-cell-differentiation-by-promoting-mitochondrial-activity
#13
Lukas Trixl, Thomas Amort, Alexandra Wille, Manuela Zinni, Susanne Ebner, Clara Hechenberger, Felix Eichin, Hanna Gabriel, Ines Schoberleitner, Anming Huang, Paolo Piatti, Roxana Nat, Jakob Troppmair, Alexandra Lusser
Chemical modifications of RNA have been attracting increasing interest because of their impact on RNA fate and function. Therefore, the characterization of enzymes catalyzing such modifications is of great importance. The RNA cytosine methyltransferase NSUN3 was recently shown to generate 5-methylcytosine in the anticodon loop of mitochondrial tRNA(Met). Further oxidation of this position is required for normal mitochondrial translation and function in human somatic cells. Because embryonic stem cells (ESCs) are less dependent on oxidative phosphorylation than somatic cells, we examined the effects of catalytic inactivation of Nsun3 on self-renewal and differentiation potential of murine ESCs...
November 4, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29099487/why-are-there-hotspot-mutations-in-the-tp53-gene-in-human-cancers
#14
REVIEW
Evan H Baugh, Hua Ke, Arnold J Levine, Richard A Bonneau, Chang S Chan
The p53 gene contains homozygous mutations in ~50-60% of human cancers. About 90% of these mutations encode missense mutant proteins that span ~190 different codons localized in the DNA-binding domain of the gene and protein. These mutations produce a protein with a reduced capacity to bind to a specific DNA sequence that regulates the p53 transcriptional pathway. Eight of these mutations are localized in codons that account for ~28% of the total p53 mutations and these alleles appear to be selected for preferentially in human cancers of many tissue types...
November 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29095713/bicuspid-aortic-valve-associated-aortopathy-update-on-biomarkers
#15
Ashna K Maredia, Steven C Greenway, Subodh Verma, Paul W M Fedak
PURPOSE OF REVIEW: Bicuspid aortic valve (BAV)-associated aortopathy is common and its progression for individual patients is difficult to predict. The present review aims to identify recent developments using biomarkers for the determination of risk and progression of disease in patients with BAV aortopathy. RECENT FINDINGS: Novel rare genetic variants and epigenetic methylation signatures affecting non-cytosine phosphate guanine (non-CpG) and CpG sites, nicotinamide phosphoribosyltransferase and Sod expression may lead to improved prediction of the aortopathy phenotype...
October 31, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/29094436/low-level-perfluorooctanoic-acid-enhances-3%C3%A2-t3-l1-preadipocyte-differentiation-via-altering-peroxisome-proliferator-activated-receptor-gamma-expression-and-its-promoter-dna-methylation
#16
Yue Ma, Jie Yang, Yanjian Wan, Yang Peng, Shuai Ding, Yuanyuan Li, Bing Xu, Xi Chen, Wei Xia, Yuebin Ke, Shunqing Xu
Recent studies suggest that perfluorooctanoic acid (PFOA) can play a role in the development of obesity; however, the associated mechanisms are poorly understood. We investigated how PFOA exposure affected the differentiation of 3 T3-L1 preadipocytes and the associated transcriptional and epigenetic mechanisms. Cells treated with different doses of PFOA (ranging from 0.01 to 100 μg ml(-1) ) were assessed for proliferation, differentiation and triglyceride accumulation. The gene expression levels of peroxisome proliferator activated receptor gamma (PPARγ) and its target genes were measured...
November 2, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29084334/association-between-brain-gene-expression-dna-methylation-and-alteration-of-ex-vivo-magnetic-resonance-imaging-transverse-relaxation-in-late-life-cognitive-decline
#17
Lei Yu, Robert J Dawe, Patricia A Boyle, Chris Gaiteri, Jingyun Yang, Aron S Buchman, Julie A Schneider, Konstantinos Arfanakis, Philip L De Jager, David A Bennett
Importance: Alteration of ex vivo magnetic resonance imaging transverse relaxation is associated with late-life cognitive decline even after controlling for common neuropathologic conditions. However, the underlying neurobiology of this association is unknown. Objective: To investigate the association between brain gene expression, DNA methylation, and alteration of magnetic resonance imaging transverse relaxation in late-life cognitive decline. Design, Setting, and Participants: Data came from 2 community-based longitudinal cohort studies of aging and dementia, the Religious Orders Study, which began in 1993, and the Rush Memory and Aging Project, which began in 1997...
October 30, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29083155/label-free-sensitive-detection-of-dna-methyltransferase-by-target-induced-hyperbranched-amplification-with-zero-background-signal
#18
Yan Zhang, Xin-Yan Wang, Qianyi Zhang, Chun-Yang Zhang
DNA methyltransferases (MTases) may specifically recognize the short palindromic sequences and transfer a methyl group from S-adenosyl-l-methionine to target cytosine/adenine. The aberrant DNA methylation is linked to the abnormal DNA MTase activity, and some DNA MTases have become promising targets of anticancer/antimicrobial drugs. However, the reported DNA MTase assays often involve laborious operation, expensive instruments, and radio-labeled substrates. Here, we develop a simple and label-free fluorescent method to sensitively detect DNA adenine methyltransferase (Dam) on the basis of terminal deoxynucleotidyl transferase (TdT)-activated Endonuclease IV (Endo IV)-assisted hyperbranched amplification...
November 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29081338/effect-of-mono-2-ethyhexyl-phthalate-on-dna-methylation-in-human-prostate-cancer-lncap-cells
#19
Jian Hui Wu, Jiao Chen, Yong Wang, Bin Xia, Rong Wang, Yan Zhao, Qin Xia Wang, Qi Song, Shun Heng Yao, Yun Hui Zhang, Zu Yue Sun
OBJECTIVE: To evaluate whether mono (2-ethylhexyl) phthalate (MEHP) affects genomic DNA methylation and the methylation status of some specific genes such as patched gene (PTCH) and smoothened gene (SMO) in LNCaP cells. METHODS: LNCaP cells were treated with MEHP (0, 1, 5, 10, and 25 μmol/L) for 3 days. An ELISA assay was preformed to detect genomic methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) content. A pyrosequencing assay was applied to assess DNA methylation in PTCH and SMO gene promoters...
September 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29073621/sexually-dimorphic-epigenetic-regulation-of-brain-derived-neurotrophic-factor-in-fetal-brain-in-the-valproic-acid-model-of-autism-spectrum-disorder
#20
Melissa A Konopko, Allison L Densmore, Bruce K Krueger
Prenatal exposure to the antiepileptic, mood-stabilizing drug, valproic acid (VPA), increases the incidence of autism spectrum disorders (ASDs); in utero administration of VPA to pregnant rodents induces ASD-like behaviors such as repetitive, stereotyped activity, and decreased socialization. In both cases, males are more affected than females. We previously reported that VPA, administered to pregnant mice at gestational day 12.5, rapidly induces a transient, 6-fold increase in BDNF (brain-derived neurotrophic factor) protein and mRNA in the fetal brain...
October 27, 2017: Developmental Neuroscience
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