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https://www.readbyqxmd.com/read/28575027/linking-epigenetic-function-to-electrostatics-the-dnmt2-structural-model-example
#1
Gilberto Cavalheiro Vieira, Gustavo Fioravanti Vieira, Marialva Sinigaglia, Vera Lúcia da Silva Valente
The amino acid sequence of DNMT2 is very similar to the catalytic domains of bacterial and eukaryotic proteins. However, there is great variability in the region of recognition of the target sequence. While bacterial DNMT2 acts as a DNA methyltransferase, previous studies have indicated low DNA methylation activity in eukaryotic DNMT2, with preference by tRNA methylation. Drosophilids are known as DNMT2-only species and the DNA methylation phenomenon is a not elucidated case yet, as well as the ontogenetic and physiologic importance of DNMT2 for this species group...
2017: PloS One
https://www.readbyqxmd.com/read/28476776/cytosine-methylation-by-dnmt2-facilitates-stability-and-survival-of-hiv-1-rna-in-the-host-cell-during-infection
#2
Rachana Roshan Dev, Rakesh Ganji, Satya Prakash Singh, Sundarasamy Mahalingam, Sharmistha Banerjee, Sanjeev Khosla
The enigmatic methyltransferase, DNMT2 (DNA methyltransferase 2), structurally resembles a DNA methyltransferase, but has been shown to be a tRNA methyltransferase targeting cytosine within a specific CpG in different tRNA molecules. We had previously shown that, during environmental stress conditions, DNMT2 is re-localized from the nucleus to the cytoplasmic stress granules (SGs) and is associated with RNA-processing proteins. In the present study, we show that DNMT2 binds and methylates various mRNA species in a sequence-independent manner and gets re-localized to SGs in a phosphorylation-dependent manner...
June 6, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28208632/cross-talk-between-dnmt2-dependent-trna-methylation-and-queuosine-modification
#3
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/28177119/downregulation-of-methyltransferase-dnmt2-results-in-condition-dependent-telomere-shortening-and-senescence-or-apoptosis-in-mouse-fibroblasts
#4
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Maciej Wnuk
Dnmt2 is a highly conserved methyltransferase of uncertain biological function(s). As Dnmt2 was considered as a driver of fruit fly longevity and a modulator of stress response, we decided to evaluate the role of Dnmt2 during stress-induced premature senescence in NIH3T3 mouse fibroblasts. Stable knockdown of Dnmt2 resulted in hydrogen peroxide-mediated sensitivity and apoptosis, whereas in the control conditions, senescence was induced. Cellular senescence was accompanied by elevated levels of p53 and p21, decreased telomere length and telomerase activity, increased production of reactive oxygen species and protein carbonylation, and DNA damage...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27819523/the-rna-methyltransferase-dnmt2-methylates-dna-in-the-structural-context-of-a-trna
#5
Steffen Kaiser, Tomasz P Jurkowski, Stefanie Kellner, Dirk Schneider, Albert Jeltsch, Mark Helm
The amino acid sequence of Dnmt2 is very similar to the catalytic domains of bacterial and eukaryotic DNA-(cytosine 5)-methyltransferases, but it efficiently catalyzes tRNA methylation, while its DNA methyltransferase activity is the subject of controversial reports with rates varying between zero and very weak. By using composite nucleic acid molecules as substrates, we surprisingly found that DNA fragments, when presented as covalent DNA-RNA hybrids in the structural context of a tRNA, can be more efficiently methylated than the corresponding natural tRNA substrate...
November 7, 2016: RNA Biology
https://www.readbyqxmd.com/read/27806111/genome-wide-analysis-of-differentially-expressed-microrna-in-bombyx-mori-infected-with-nucleopolyhedrosis-virus
#6
Ping Wu, Xiaoxu Jiang, Xijie Guo, Long Li, Tao Chen
Bombyx mori nucleopolyhedrosis virus (BmNPV) is a major pathogen that threatens the growth and sustainability of the sericulture industry. Since microRNAs (miRNAs) have been shown to play important roles in host-pathogen interactions, in this study we investigated the effects of BmNPV infection on silkworm microRNAs expression profile. To achieve this, we constructed and deep-sequenced two small RNA libraries generated from BmNPV infected and un-infected larvae. The results revealed that 38 silkworm miRNAs were differentially expressed after BmNPV infection...
2016: PloS One
https://www.readbyqxmd.com/read/27805064/comprehensive-dna-methylation-analysis-of-the-aedes-aegypti-genome
#7
Cassandra Falckenhayn, Vitor Coutinho Carneiro, Anderson de Mendonça Amarante, Katharina Schmid, Katharina Hanna, Seokyoung Kang, Mark Helm, George Dimopoulos, Marcelo Rosado Fantappié, Frank Lyko
Aedes aegypti mosquitoes are important vectors of viral diseases. Mosquito host factors play key roles in virus control and it has been suggested that dengue virus replication is regulated by Dnmt2-mediated DNA methylation. However, recent studies have shown that Dnmt2 is a tRNA methyltransferase and that Dnmt2-dependent methylomes lack defined DNA methylation patterns, thus necessitating a systematic re-evaluation of the mosquito genome methylation status. We have now searched the Ae. aegypti genome for candidate DNA modification enzymes...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27687053/dna-methyltransferases-exhibit-dynamic-expression-during-spermatogenesis
#8
REVIEW
Fatma Uysal, Gokhan Akkoyunlu, Saffet Ozturk
DNA methylation is one of the epigenetic marks and plays critically important functions during spermatogenesis in mammals. DNA methylation is catalysed by DNA methyltransferase (DNMT) enzymes, which are responsible for the addition of a methyl group to the fifth carbon atom of the cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites. Structurally and functionally five different DNMT enzymes have been identified in mammals, including DNMT1, DNMT2, DNMT3A, DNMT3B and DNMT3L...
December 2016: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/27659861/cytotoxic-and-cytostatic-side-effects-of-chitosan-nanoparticles-as-a-non-viral-gene-carrier
#9
Gizem Bor, Jennifer Mytych, Jacek Zebrowski, Maciej Wnuk, Gülşah Şanlı-Mohamed
Although chitosan nanoparticles (CNs) became a promising tool for several biological and medical applications owing to their inherent biocompatibility and biodegradability features, studies regarding their effects on cytotoxic and cytostatic properties still remain insufficient. Therefore, in the present study, we decided to perform comprehensive analysis of the interactions between CNs-pKindling-Red-Mito (pDNA) and different cell line models derived from blood system and human solid tissues cancers. The resulting CNs-pDNA was investigated in terms of their cellular uptake, transfection efficiency, and physico-chemical, cytotoxic and cytostatic properties...
November 20, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27281847/-dnmt2-is-the-most-evolutionary-conserved-and-enigmatic-cytosine-dna-methyltransferase-in-eukaryotes
#10
REVIEW
V V Ashapkin, L I Kutueva, B F Vanyushin
Dnmt2 is the most strongly conserved cytosine DNA methyltransferase in eukaryotes. It has been found in all organisms possessing methyltransferases of the Dnmt1 and Dnmt3 families, whereas in many others Dnmt2 is the sole cytosine DNA methyltransferase. The Dnmt2 molecule contains all conserved motifs of cytosine DNA methyltransferases. It forms 3D complexes with DNA very similar to those of bacterial DNA methyltransferases and performs cytosine methylation by a catalytic mechanism common to all cytosine DNA methyltransferases...
March 2016: Genetika
https://www.readbyqxmd.com/read/27270731/dnmt2-trdmt1-as-mediator-of-rna-polymerase-ii-transcriptional-activity-in-cardiac-growth
#11
Hossein Ghanbarian, Nicole Wagner, Beatrice Polo, Delphine Baudouy, Jafar Kiani, Jean-François Michiels, François Cuzin, Minoo Rassoulzadegan, Kay-Dietrich Wagner
Dnmt2/Trdmt1 is a methyltransferase, which has been shown to methylate tRNAs. Deficient mutants were reported to exhibit various, seemingly unrelated, defects in development and RNA-mediated epigenetic heredity. Here we report a role in a distinct developmental regulation effected by a noncoding RNA. We show that Dnmt2-deficiency in mice results in cardiac hypertrophy. Echocardiographic measurements revealed that cardiac function is preserved notwithstanding the increased dimensions of the organ due to cardiomyocyte enlargement...
2016: PloS One
https://www.readbyqxmd.com/read/27260394/plant-dna-methyltransferase-genes-multiplicity-expression-methylation-patterns
#12
V V Ashapkin, L I Kutueva, B F Vanyushin
Expression and methylation patterns of genes encoding DNA methyltransferases and their functionally related proteins were studied in organs of Arabidopsis thaliana plants. Genes coding for the major maintenance-type DNA methyltransferases, MET1 and CMT3, and the major de novo-type DNA methyltransferase, DRM2, are actively expressed in all organs. Similar constitutively active expression was observed for genes encoding their functionally related proteins, a histone H3K9 methyltransferase KYP and a catalytically non-active protein DRM3...
February 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27232191/mechanism-and-biological-role-of-dnmt2-in-nucleic-acid-methylation
#13
Albert Jeltsch, Ann Ehrenhofer-Murray, Tomasz P Jurkowski, Frank Lyko, Gunter Reuter, Serge Ankri, Wolfgang Nellen, Matthias Schaefer, Mark Helm
A group of homologous nucleic acid modification enzymes called Dnmt2, Trdmt1, Pmt1, DnmA, and Ehmet in different model organisms catalyze the transfer of a methyl group from the cofactor S-adenosyl-methionine (SAM) to the carbon-5 of cytosine residues. Originally considered as DNA MTases, these enzymes were shown to be tRNA methyltransferases about a decade ago. Between the presumed involvement in DNA modification-related epigenetics, and the recent foray into the RNA modification field, significant progress has characterized Dnmt2-related research...
May 27, 2016: RNA Biology
https://www.readbyqxmd.com/read/26909551/aging-is-associated-with-hypermethylation-of-autophagy-genes-in-macrophages
#14
Hany Khalil, Mia Tazi, Kyle Caution, Amr Ahmed, Apurva Kanneganti, Kaivon Assani, Benjamin Kopp, Clay Marsh, Duaa Dakhlallah, Amal O Amer
Autophagy is a biological process characterized by self-digestion and involves induction of autophagosome formation, leading to degradation of autophagic cargo. Aging is associated with the reduction of autophagy activity leading to neurodegenerative disorders, chronic inflammation, and susceptibility to infection; however, the underlying mechanism is unclear. DNA methylation by DNA methyltransferases reduces the expression of corresponding genes. Since macrophages are major players in inflammation and defense against infection we determined the differences in methylation of autophagy genes in macrophages derived from young and aged mice...
May 3, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/26843106/prolonged-effects-of-silver-nanoparticles-on-p53-p21-pathway-mediated-proliferation-dna-damage-response-and-methylation-parameters-in-ht22-hippocampal-neuronal-cells
#15
Jennifer Mytych, Jacek Zebrowski, Anna Lewinska, Maciej Wnuk
It is widely accepted that silver nanoparticles (AgNPs) are toxic to biological systems. However, little is known about their actions at molecular level and the cytophysiological effects after AgNP removal. As nanoparticles are suggested a promising tool to transport drugs to the brain for use in neurological conditions, we used HT22 mouse hippocampal neuronal cells as a model to study AgNP-mediated effects after their removal from the cell culture medium. We selected a relatively low concentration of AgNPs, 5 μg/ml, treated the cells for 48 h, and evaluated AgNP-induced cytophysiological effects after 96 h of AgNP removal...
March 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/26843075/the-role-of-dna-methylation-during-anoxia-tolerance-in-a-freshwater-turtle-trachemys-scripta-elegans
#16
Sanoji Wijenayake, Kenneth B Storey
Oxygen deprivation is a lethal stress that only a few animals can tolerate for extended periods. This study focuses on analyzing the role of DNA methylation in aiding natural anoxia tolerance in a champion vertebrate anaerobe, the red-eared slider turtle (Trachemys scripta elegans). We examined the relative expression and total enzymatic activity of four DNA methyltransferases (DNMT1, DNMT2, DNMT3a and DNMT3b), two methyl-binding domain proteins (MBD1 and MBD2), and relative genomic levels of 5-methylcytosine under control, 5 h anoxic, and 20 h anoxic conditions in liver, heart, and white skeletal muscle (n = 4, p < 0...
April 2016: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/26814705/low-doses-of-nanodiamonds-and-silica-nanoparticles-have-beneficial-hormetic-effects-in-normal-human-skin-fibroblasts-in-culture
#17
Jennifer Mytych, Maciej Wnuk, Suresh I S Rattan
Nanodiamonds (ND) and silica nanoparticles (SiO2-NP) have been much investigated for their toxicity at high doses, little is known about their biological activity at low concentrations. Here we report the biphasic dose response of ND and SiO2-NP in modulating normal human facial skin fibroblasts (FSF1) in culture. ND and SiO2-NP at low concentration (up to 0.5 μg/ml) had beneficial effects on FSF1 in terms of increasing their proliferation and metabolic activity. Exposure of FSF1 cells to low levels of NP enhanced their wound healing ability in vitro and slowed down aging during serial passaging as measured by maintenance of youthful morphology, reduction in the rate of loss of telomeres, and the over all proliferative characteristics...
April 2016: Chemosphere
https://www.readbyqxmd.com/read/26639858/physcomitrella-patens-dna-methyltransferase-2-is-required-for-recovery-from-salt-and-osmotic-stress
#18
Deepshikha Arya, Sanjay Kapoor, Meenu Kapoor
DNA methyltransferase 2 (DNMT2) unlike other members of the cytosine DNA methyltransferase gene family has dual substrate specificity and it methylates cytosines in both the DNA and transfer RNA (tRNA). Its role in plants, however, has remained obscure to date. In this study, we demonstrate that DNMT2 from Physcomitrella patens accumulates in a temporal manner under salt and osmotic stress showing maximum accumulation during recovery, i.e. 24 h after plants are transferred to normal growth medium. Therefore, to study its role in stress tolerance, we generated PpDNMT2 targeted knockout plants (ppdnmt2ko)...
February 2016: FEBS Journal
https://www.readbyqxmd.com/read/26424849/dynamic-modulation-of-dnmt2-dependent-trna-methylation-by-the-micronutrient-queuine
#19
Martin Müller, Mark Hartmann, Isabelle Schuster, Sebastian Bender, Kathrin L Thüring, Mark Helm, Jon R Katze, Wolfgang Nellen, Frank Lyko, Ann E Ehrenhofer-Murray
Dnmt2 enzymes are cytosine-5 methyltransferases that methylate C38 of several tRNAs. We report here that the activities of two Dnmt2 homologs, Pmt1 from Schizosaccharomyces pombe and DnmA from Dictyostelium discoideum, are strongly stimulated by prior queuosine (Q) modification of the substrate tRNA. In vivo tRNA methylation levels were stimulated by growth of cells in queuine-containing medium; in vitro Pmt1 activity was enhanced on Q-containing RNA; and queuine-stimulated in vivo methylation was abrogated by the absence of the enzyme that inserts queuine into tRNA, eukaryotic tRNA-guanine transglycosylase...
December 15, 2015: Nucleic Acids Research
https://www.readbyqxmd.com/read/26271101/the-trna-methyltransferase-dnmt2-is-required-for-accurate-polypeptide-synthesis-during-haematopoiesis
#20
Francesca Tuorto, Friederike Herbst, Nader Alerasool, Sebastian Bender, Oliver Popp, Giuseppina Federico, Sonja Reitter, Reinhard Liebers, Georg Stoecklin, Hermann-Josef Gröne, Gunnar Dittmar, Hanno Glimm, Frank Lyko
The Dnmt2 enzyme utilizes the catalytic mechanism of eukaryotic DNA methyltransferases to methylate several tRNAs at cytosine 38. Dnmt2 mutant mice, flies, and plants were reported to be viable and fertile, and the biological function of Dnmt2 has remained elusive. Here, we show that endochondral ossification is delayed in newborn Dnmt2-deficient mice, which is accompanied by a reduction of the haematopoietic stem and progenitor cell population and a cell-autonomous defect in their differentiation. RNA bisulfite sequencing revealed that Dnmt2 methylates C38 of tRNA Asp(GTC), Gly(GCC), and Val(AAC), thus preventing tRNA fragmentation...
September 14, 2015: EMBO Journal
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