Search results for "cytosine"
showing 10 items of 117 documents
Expression ofDNMT3A transcripts and nucleolar localization of DNMT3A protein in human testicular and fibroblast cells suggest a role for de novo DNA …
2006
Transcriptional silencing during differentiation of human male germ cells and serum starvation of human fibroblasts is controlled by epigenetic mechanisms that involve de novo DNA methylation. It is associated with high expression of different transcripts of the DNA methyltransferase 3A (DNMT3A) gene that encode two isoforms with de novo methyltransferase activity and one without catalytic activity. Western blots revealed that DNMT3A protein (with catalytic domain) is present at low levels in several tissues and at increased levels in testicular cells and growth-arrested fibroblasts. Immunofluorescence experiments localized DNMT3A to discrete nucleolar foci in B spermatogonia and resting fi…
PURINE AND PYRIMIDINE NUCLEOTIDES IN THE BRAIN OF NORMAL AND CONVULSANT RATS
1969
— Purine and pyrimidine nucleotides were measured in the brain of normal and electroshocked rats after chromatographic separation on ion-exchange resin of mono-, di- and tri-phosphorylated derivatives. CMP, IMP and NAD did not show any significant quantitative change. Adenine nucleotides showed an abrupt change followed by a rapid return to the control value. GTP was the only purine nucleotide exhibiting a relatively slow return to its starting concentration. The greatest percentage increase after electroshock was observed in UMP, which returned to its control value only after 5 min; UDPCoenzymes (i.e. UDPA plus UDPG) showed a relatively small drop during the development of the seizure and …
RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis.
2012
The function of cytosine-C5 methylation, a widespread modification of tRNAs, has remained obscure, particularly in mammals. We have now developed a mouse strain defective in cytosine-C5 tRNA methylation, by disrupting both the Dnmt2 and the NSun2 tRNA methyltransferases. Although the lack of either enzyme alone has no detectable effects on mouse viability, double mutants showed a synthetic lethal interaction, with an underdeveloped phenotype and impaired cellular differentiation. tRNA methylation analysis of the double-knockout mice demonstrated complementary target-site specificities for Dnmt2 and NSun2 and a complete loss of cytosine-C5 tRNA methylation. Steady-state levels of unmethylate…
RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage
2010
The covalent modification of nucleic acids plays an important role in regulating the functions of DNA and RNA. DNA modifications have been analyzed in considerable detail, and the characterization of (cytosine-5) DNA methylation has been crucial for understanding the molecular basis of epigenetic gene regulation (Klose and Bird 2006). (Cytosine-5) methylation has also been documented in various RNA species, including tRNA, but the function of RNA methylation has not been firmly established yet (Motorin et al. 2010). Dnmt2 proteins were originally assigned to the DNA methyltransferase family, because of their strong sequence conservation of catalytic DNA methyltransferase motifs (Okano et al…
The C(-260)T gene polymorphism in the promoter of the CD14 monocyte receptor gene is not associated with acute myocardial infarction.
2003
CD surface molecules mediates cell activation and signaling. In particular, CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide. Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis. It has been recently shown that a C(-260)T polymorphism in the promoter of the CD14 receptor may be a risk factor for coronary artery disease. Recently this association has been questioned because no increased risk was found with the T allele, even in the homozygous state. In the present study we investigated a possible association between the C(-260)T polymorphism in the CD14 promoter and acute myocardial infarction. Two hundred and thrteen patients …
Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5 variants: the GOLDN study.
2007
Objective— Apolipoprotein A5 ( APOA5 ) is a key determinant of plasma triglyceride (TG) concentrations. Genetic variation at the APOA5 locus could be responsible for some of the observed differences in response to fenofibrate therapy. Methods and Results— We examined the association between tag SNPs (−1131T>C and 56C>G) at APOA5 and TG and HDL-C response to fenofibrate and a postprandial lipid challenge in 791 men and women participating in the GOLDN study. After 3-week drug treatment, APOA5 56G carriers displayed significant decrease in TG ( P =0.006), and increase in HDL-C ( P =0.002) levels relative to their basal values in the fasting state when compared with noncarriers (a TG re…
Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to subchronic variable stress
2015
Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differe…
Substrate promiscuity in DNA methyltransferase M.PvuII. A mechanistic insight
2012
M.PvuII is a DNA methyltransferase from the bacterium Proteus vulgaris that catalyzes methylation of cytosine at the N4 position. This enzyme also displays promiscuous activity catalyzing methylation of adenine at the N6 position. In this work we use QM/MM methods to investigate the reaction mechanism of this promiscuous activity. We found that N6 methylation in M.PvuII takes place by means of a stepwise mechanism in which deprotonation of the exocyclic amino group is followed by the methyl transfer. Deprotonation involves two residues of the active site, Ser53 and Asp96, while methylation takes place directly from the AdoMet cofactor to the target nitrogen atom. The same reaction mechanism…
A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Act…
2009
Cytosine-5 methyltransferases of the Dnmt2 family function as DNA and tRNA methyltransferases. Insight into the role and biological significance of Dnmt2 is greatly hampered by a lack of knowledge about its protein interactions. In this report, we address the subject of protein interaction by identifying enolase through a yeast two-hybrid screen as a Dnmt2-binding protein. Enolase, which is known to catalyze the conversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), was shown to have both a cytoplasmatic and a nuclear localization in the parasite Entamoeba histolytica. We discovered that enolase acts as a Dnmt2 inhibitor. This unexpected inhibitory activity was antagonized by…
Unraveling the Reaction Mechanism of Enzymatic C5-Cytosine Methylation of DNA. A Combined Molecular Dynamics and QM/MM Study of Wild Type and Gln119 …
2016
M.HhaI is a DNA methyltransferase from Haemophilus hemolyticus that catalyzes the transfer of a methyl group from S-adenosyl-l-methionine (SAM) to the C5 position of a cytosine. This enzyme is a paradigmatic model for C5 DNA methyltransferases due to its major homology to mammalian enzymes and to the availability of high-resolution structures of the DNA–enzyme complex. In spite of the number of experimental and theoretical analyses carried out for this system, many mechanistic details remain unraveled. We have used full atomistic classical molecular dynamics simulations to explore the protein–SAM–DNA ternary complex, where the target cytosine base is flipped out into the active site for bot…