Search results for "METHYLATION"
showing 10 items of 607 documents
The DNA methylation inhibitor 5-azacytidine modulates 6-thioguanine toxicity in mammalian cells
2003
In order to assess the effects of combining two antimetabolites used separately to treat human leukemias, we carried out an experimental study by exposing V79 Chinese hamster cells, a 6-thioguanine (6-tG)-sensitive cell line, to sequential and concurrent treatments with 5-azacytidine (5-azaC) and 6-tG. In this paper, we demonstrate that there is a clear dependency for the way in which this combination was tested. Pre-treatment with 5-azaC made V79 cells more resistant to 6-tG by a substantial reduction in 6-tG incorporation into DNA; this effect could still be detected for several cell divisions after the removal of 5-azaC, and was achieved neither by reduced cell growth nor by the inductio…
Effect of antibodies against cytochrome P-450 on demethylation and denitrosation of N-nitrosodimethylamine and N-nitrosomethylaniline.
1988
Rat liver microsomes which were induced either with ethanol or PB were incubated with NDMA or NMA. Formaldehyde generation and nitrite formation were measured as metabolic parameters for oxidative bioactivation and denitrosation, respectively. The influence of antiserum PB3a1 and PB22 containing antibodies against the corresponding cytochrome P-450 species on both metabolic functions was investigated. The results showed that the influence on formaldehyde production and denitrosation varied independently in that both parameters were either not affected, or influenced in an opposite way, or inhibited to a different degree. Especially remarkable was the 80% inhibition of formaldehyde generatio…
Non-Innocent Base Properties of 3- and 4-Pyridyl-dithia- and Diselenadiazolyl Radicals : The Effect of N-Methylation
2018
International audience; Condensation of persilylated nicotinimideamide and isonicotinimideamide with sulfur monochloride affords double salts of the 3-, 4-pyridyl-substituted 1,2,3,5-dithiadiazolylium DTDA cations of the general formula [3-, 4-pyDTDA][Cl][HCl] in which the pyridyl nitrogen serves as a noninnocent base. Reduction of these salts with triphenylantimony followed by deprotonation of the intermediate-protonated radical affords the free base radicals [3-, 4-pyDTDA], the crystal structures of which, along with those of their diselenadiazolyl analogues [3-, 4-pyDSDA], have been characterized by powder or single-crystal X-ray diffraction. The crystal structures consist of “pancake” π…
Beckwith–Wiedemann syndrome: multiple molecular mechanisms
2006
Beckwith–Wiedemann syndrome (BWS) is a congenital overgrowth condition with an increased risk of developing embryonic tumours, such as Wilms' tumour. The cardinal features are abdominal wall defects, macroglossia and gigantism. BWS is generally sporadic; only 10–15% of cases are familial. A variety of molecular aberrations have been associated with BWS. The only mutations within a gene are loss-of-function mutations in the CDKN1C gene, which codes for an imprinted cell-cycle regulator. CDKN1C mutations appear to be particularly associated with umbilical abnormalities, but not with increased predisposition to Wilms' tumour. In the remaining BWS subgroups, a disturbance of the tight epigeneti…
Hybrid Quantum Mechanics/Molecular Mechanics Simulations with Two-Dimensional Interpolated Corrections: Application to Enzymatic Processes
2006
Hybrid quantum mechanics/molecular mechanics (QM/MM) techniques are widely used to study chemical reactions in large systems. Because of the computational cost associated with the high dimensionality of these systems, the quantum description is usually restricted to low-level methods, such as semiempirical Hamiltonians. In some cases, the description obtained at this computational level is quite poor and corrections must be considered. We here propose a simple but efficient way to include higher-level corrections to be used in potential energy surface explorations and in the calculation of potentials of mean force. We evaluate a correction energy term as the difference between a high-level …
Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas
2007
AbstractIntegrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them w…
Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification.
2015
Mechanisms of initial cell fate decisions differ among species. To gain insights into lineage allocation in humans, we derived ten human embryonic stem cell lines (designated UCSFB1-10) from single blastomeres of four 8-cell embryos and one 12-cell embryo from a single couple. Compared with numerous conventional lines from blastocysts, they had unique gene expression and DNA methylation patterns that were, in part, indicative of trophoblast competence. At a transcriptional level, UCSFB lines from different embryos were often more closely related than those from the same embryo. As predicted by the transcriptomic data, immunolocalization of EOMES, T brachyury, GDF15 and active β-catenin reve…
Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes
2020
Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA methylation in drug-naïve patients with T2D at the time of their diagnosis. DNA methylation of 11 and 4 sites differed between glycemic responders/nonresponders and metformin-tolerant/intolerant patients, respectively, in discovery and replication cohorts. Greater methylation at these sites associ…
DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific.
2000
Methionine adenosyltransferase (MAT) catalyzes the biosynthesis of S-adenosylmethionine (AdoMet). In mammals MAT activity derives from two separate genes which display a tissue-specific pattern of expression. While MAT1A is expressed only in the adult liver, MAT2A is expressed in non-hepatic tissues. The mechanisms behind the selective expression of these two genes are not fully understood. In the present report we have evaluated MAT1A and MAT2A methylation in liver and in other tissues, such as kidney, by methylation-sensitive restriction enzyme digestion of genomic DNA. Our data indicate that MAT1A is hypomethylated in liver and hypermethylated in non-expressing tissues. The opposite situ…
Phosphorylation Regulates CIRBP Arginine Methylation, Transportin-1 Binding and Liquid-Liquid Phase Separation
2021
Arginine-glycine(-glycine) (RG/RGG) regions are highly abundant in RNA-binding proteins and involved in numerous physiological processes. Aberrant liquid-liquid phase separation (LLPS) and stress granule (SGs) association of RG/RGG regions in the cytoplasm have been implicated in several neurodegenerative disorders. LLPS and SG association of these proteins is regulated by the interaction with nuclear import receptors, such as transportin-1 (TNPO1), and by post-translational arginine methylation. Strikingly, many RG/RGG proteins harbour potential phosphorylation sites within or close to their arginine methylated regions, indicating a regulatory role. Here, we studied the role of phosphoryla…