Methylome analysis of deoxyadenosines in higher eukaryotes
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: MTBLS276PRJNA299278
ORGANISM(S): Xenopus laevis Mus musculus Escherichia coli
PROVIDER: GSE74184 | GEO | 2015/11/12
SECONDARY ACCESSION(S): PRJNA299278
REPOSITORIES: GEO
Similar Datasets
Project description:Since the discovery that cytosine deoxynucleotides could be methylated (dC5m), not much is known in higher eukaryotes about modifications affecting other deoxynucleotides. Here, we now report that we detected N-6-methyl-deoxyadenosine (dA6m) not only in frog DNA, but also in other species including mouse and human. Our methylome analysis revealed that dA6m is widely distributed across the eukaryotic genome, is present in different cell types, but commonly depleted from gene exons. Since dA6m is a direct modification of DNA, it has the potential to generate a significant impact on different biological areas. Ultimately, our work shows that deoxycytidine modifications might not be the only ones in higher eukaryotes, suggesting that such direct DNA modifications might be more widespread than previously thought.
2015-11-16 | MTBLS276 | MetaboLights
Project description:This data set was downloaded from MetaboLights (http://www.ebi.ac.uk/metabolights/) accession number MTBLS276 Abstract:"Since the discovery that cytosine deoxynucleotides could be methylated (dC5m), not much is known in higher eukaryotes about modifications affecting other deoxynucleotides. Here, we now report that we detected N-6-methyl-deoxyadenosine (dA6m) not only in frog DNA, but also in other species including mouse and human. Our methylome analysis revealed that dA6m is widely distributed across the eukaryotic genome, is present in different cell types, but commonly depleted from gene exons. Since dA6m is a direct modification of DNA, it has the potential to generate a significant impact on different biological areas. Ultimately, our work shows that deoxycytidine modifications might not be the only ones in higher eukaryotes, suggesting that such direct DNA modifications might be more widespread than previously thought."
2018-08-07 | MSV000082792 | GNPS
Project description:Methylome analysis of deoxyadenosines in higher eukaryotes
| PRJNA299278 | ENA
Project description:DNA methylation is a key mechanism for regulation of DNA repair, DNA replication, and gene expression. In bacteria, DNA is modified by methylation on C5-cytosine (5mC), N6-adenine (6mA) and N4-cytosine (4mC). Metazoans were thought to only use 5mC to regulate gene expression until the recent discovery of N6-adenine methylation in DNA of diverse metazoan species, including mammals. Here we show by dot blot, immunoprecipitation with 4mC-specific antibodies, and ultra-high performance liquid chromatography coupled with triple-quadrupole mass spectrometry that 4mC also occurs in most eukaryotes. We further characterize 4mC sites on a near genome-wide scale by single molecule real time (SMRT) sequencing in the nematode C. elegans. In C. elegans, 4mC is found in all chromosomes but is relatively sparse on the X chromosome. 4mC is relatively enriched on introns, depleted on exons, and co-localizes with 6mA. In human cells, 4mC is anti-correlated with 5mC. Moreover, 4mC modifications are associated with increased gene expression. Transfection of human cells with a 4mC-modified luciferase reporter plasmid increases luciferase expression as compared to the unmethylated plasmid. These data suggest that 4mC promotes gene transcription, playing an opposing role to 5mC, which generally represses transcription. Thus 4mC modification of DNA is a previously unrecognized mechanism of gene regulation in eukaryotes, providing evidence for a complex epigenetic DNA code.
2018-09-01 | GSE86993 | GEO
Project description:From bacteria to plants and humans, the glutathione system plays a pleiotropic role in cell defense against metabolic, oxidative and metal stresses. Glutathione (GSH), the γ-L-glutamyl-L-cysteinyl-glycine nucleophile tri-peptide, is the central player of this system that acts in redox homeostasis, detoxification and iron metabolism in most living organisms. GSH directly scavenges diverse reactive oxygen species (ROS), such as singlet oxygen, superoxide anion, hydrogen peroxide, hydroxyl radical, nitric oxide and carbon radicals. It also serves as a cofactor for various enzymes, such as glutaredoxins (Grxs), glutathione peroxidases (Gpxs), glutathione reductase (GR) and glutathione-S-transferases (GSTs), which play crucial roles in cell detoxication. This review summarizes what is known concerning the GSH-system (GSH, GSH-derived metabolites and GSH-dependent enzymes) in selected model organisms (Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana and human), emphasizing cyanobacteria for the following reasons. Cyanobacteria are environmentally crucial and biotechnologically important organisms that are regarded as having evolved photosynthesis and the GSH system to protect themselves against the ROS produced by their active photoautotrophic metabolism. Furthermore, cyanobacteria synthesize the GSH-derived metabolites, ergothioneine and phytochelatin, that play crucial roles in cell detoxication in humans and plants, respectively. Cyanobacteria also synthesize the thiol-less GSH homologs ophthalmate and norophthalmate that serve as biomarkers of various diseases in humans. Hence, cyanobacteria are well-suited to thoroughly analyze the role/specificity/redundancy of the players of the GSH-system using a genetic approach (deletion/overproduction) that is hardly feasible with other model organisms (E. coli and S. cerevisiae do not synthesize ergothioneine, while plants and humans acquire it from their soil and their diet, respectively).
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Project description:Disease-associated misfolded proteins or proteins damaged due to cellular stress are generally disposed via the cellular protein quality-control system. However, under saturating conditions, misfolded proteins will aggregate. In higher eukaryotes, these aggregates can be transported to accumulate in aggresomes at the microtubule organizing center. The fate of cells that contain aggresomes is currently unknown. Here we report that cells that have formed aggresomes can undergo normal mitosis. As a result, the aggregated proteins are asymmetrically distributed to one of the daughter cells, leaving the other daughter free of accumulated protein damage. Using both epithelial crypts of the small intestine of patients with a protein folding disease and Drosophila melanogaster neural precursor cells as models, we found that the inheritance of protein aggregates during mitosis occurs with a fixed polarity indicative of a mechanism to preserve the long-lived progeny.
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Project description:Evolutionary conserved mitochondrial nucleases are involved in programmed cell death and normal cell proliferation in lower and higher eukaryotes. The endo/exonuclease Nuc1p, also termed 'yeast Endonuclease G (EndoG)', is a member of this class of enzymes that differs from mammalian homologs by the presence of a 5'-3' exonuclease activity in addition to its broad spectrum endonuclease activity. However, this exonuclease activity is thought to be essential for a function of the yeast enzyme in DNA recombination and repair. Here we show that higher eukaryotes in addition to EndoG contain its paralog 'EXOG', a novel EndoG-like mitochondrial endo/exonuclease. We find that during metazoan evolution duplication of an ancestral nuclease gene obviously generated the paralogous EndoG- and EXOG-protein subfamilies in higher eukaryotes, thereby maintaining the full endo/exonuclease activity found in mitochondria of lower eukaryotes. We demonstrate that human EXOG is a dimeric mitochondrial enzyme that displays 5'-3' exonuclease activity and further differs from EndoG in substrate specificity. We hypothesize that in higher eukaryotes the complementary enzymatic activities of EndoG and EXOG probably together account for both, the lethal and vital functions of conserved mitochondrial endo/exonucleases.
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Project description:Nuclear pore complexes have recently been shown to play roles in gene activation; however their potential involvement in metazoan transcription remains unclear. Here we show that the nucleoporins Sec13, Nup98, and Nup88, as well as a group of FG-repeat nucleoporins, bind to the Drosophila genome at functionally distinct loci that often do not represent nuclear envelope contact sites. Whereas Nup88 localizes to silent loci, Sec13, Nup98, and a subset of FG-repeat nucleoporins bind to developmentally regulated genes undergoing transcription induction. Strikingly, RNAi-mediated knockdown of intranuclear Sec13 and Nup98 specifically inhibits transcription of their target genes and prevents efficient reactivation of transcription after heat shock, suggesting an essential role of NPC components in regulating complex gene expression programs of multicellular organisms.
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Project description:The first step of iron biomineralization mediated by ferritin is the oxidation at the ferroxidase active site of two ferrous ions to a diferric oxo/hydroxo species. Metal-loaded ferritin crystals obtained by soaking crystals of frog ferritin in FeSO(4) and CuSO(4) solutions followed by flash freezing provided X-ray crystal structures of the tripositive iron and bipositive copper adducts at 2.7 and 2.8 Å resolution, respectively. At variance with the already available structures, the crystal form used in this study contains 24 independent subunits in the asymmetric unit permitting comparison between them. For the first time, the diferric species at the ferroxidase site is identified in ferritins from higher eukaryotes. Anomalous difference Fourier maps for crystals (iron crystal 1) obtained after long soaking times in FeSO(4) solution invariantly showed diferric species with a Fe-Fe average distance of 3.1 ± 0.1 Å, strongly indicative of the presence of a ?-oxo/hydroxo bridge between the irons; protein ligands for each iron ion (Fe1 and Fe2) were also unequivocally identified and found to be the same in all subunits. For copper bound ferritin, dicopper(II) centers are also observed. While copper at site 1 is essentially in the same position and has the same coordination environment as Fe1, copper at site 2 is displaced toward His54, now acting as a ligand; this results in an increased intermetal distance (4.3 ± 0.4 Å). His54 coordination and longer metal-metal distances might represent peculiar features of divalent cations at the ferroxidase site. This oxidation-dependent structural information may provide key features for the mechanistic pathway in ferritins from higher eukaryotes that drive uptake of bivalent cation and release of ferric products at the catalytic site. This mechanism is supported by the X-ray picture obtained after only 1 min of soaking in FeSO(4) solutions (iron crystal 2) which reasonably contain the metal at different oxidation states. Here two different di-iron species are trapped in the active site, with intermetal distances corresponding to those of the ferric dimer in crystal 1 and of the dicopper centers and corresponding rearrangement of the His54 side chain.
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