Search results for " hypomethylation"
showing 10 items of 13 documents
DNA demethylation caused By 5-Aza-2'-Deoxycytidine induces mitotic alterations and aneuploidy
2016
Aneuploidy, the unbalanced number of chromosomes in a cell, is considered a prevalent form of genetic instability and is largely acknowledged as a condition implicated in tumorigenesis. Epigenetic alterations like DNA hypomethylation have been correlated with cancer initiation/progression. Furthermore, a growing body of evidence suggests the involvement of epigenome-wide disruption as a cause of global DNA hypomethylation in aneuploidy generation. Here, we report that the DNA hypomethylating drug 5-aza-2′-deoxycytidine (DAC), affects the correct ploidy of nearly diploid HCT-116 human cells by altering the methylation pattern of the chromosomes. Specifically, we show that a DAC-induced reduc…
DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progr…
2016
Abstract Aging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, a…
Dysregulation of DNA methylation induced by past arsenic treatment causes persistent genomic instability in mammalian cells
2015
The mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. To investigate potential epigenetic mechanisms, in this study we evaluated global DNA methylation levels in V79 cells and human HaCaT keratinocytes at several time points during expanded growth of cell cultures following removal of arsenite exposures. We have found altered genomic methylation patterns that persisted up to 40 cell generations in HaCaT cells after the treatments were withdrawn. Moreover, mRNA expression levels were evaluated by RT-PCR for DNMT1, DNMT3A, DNMT3B, HMLH1, and HMSH2 genes, demonstrating that the down regulation of DNMT3A and DNMT3B genes, but not DNMT1, o…
Esophageal atresia and Beckwith–Wiedemann syndrome in one of the naturally conceived discordant newborn twins: first report
2018
Key Clinical Message Recent studies report a high incidence of monozygotic twinning in Beckwith–Wiedemann syndrome. A phenotypical discordance in monozygotic twins is rare. Twinning and Beckwith–Wiedemann syndrome show higher incidence in children born after assisted reproductive techniques. We report on the first observation of esophageal atresia and Beckwith–Wiedemann syndrome in one of the naturally conceived discordant monozygotic twins.
DNA methylation patterns in newborns exposed to tobacco in utero
2015
[Background] Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth.
Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cells
2004
Early genetic instability induced in dividing V79-Cl3 Chinese hamster cells by inorganic arsenic, as demonstrated in our previous investigation, was evidenced by aneuploidy and nuclear abnormalities, but not by chromosomal rearrangements. Here we report the results of cytogenetic and morphological analyses performed on the progeny of cells dividing at the end of sodium arsenite treatment after they had been expanded through 120 generations (ASO cells) and then cloned. The acquired genetic instability persisted and was increased by highly unstable chromosomal rearrangements, namely dicentric chromosomes and telomeric associations, which were not seen following acute exposure. A peculiar find…
The Histone Deacetylase Inhibitor JAHA Down-Regulates pERK and Global DNA Methylation in MDA-MB231 Breast Cancer Cells
2015
The histone deacetylase inhibitor N-1-(ferrocenyl)-N-8-hydroxyoctanediamide (JAHA) down-regulates extracellular-signal-regulated kinase (ERK) and its activated form in triple-negative MDA-MB231 breast cancer cells after 18 h and up to 30 h of treatment, and to a lesser extent AKT and phospho-AKT after 30 h and up to 48 h of treatment. Also, DNA methyltransferase 1 (DNMT1), 3b and, to a lesser extent, 3a, downstream ERK targets, were down-regulated already at 18 h with an increase up to 48 h of exposure. Methylation-sensitive restriction arbitrarily-primed (MeSAP) polymerase chain reaction (PCR) analysis confirmed the ability of JAHA to induce genome-wide DNA hypomethylation at 48 h of expos…
Losing DNA methylation at repetitive elements and breaking bad
2021
Abstract Background DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability (including chromosome stability) by controlling both gene expression and chromatin structure. Therefore, the onset of an incorrect pattern of DNA methylation is potentially dangerous for the cells. This is particularly important with respect to repetitive elements, which constitute the third of the human genome. Main body Repetitive sequences are involved in several cell processes, however, due to their intrinsic nature, they can be a source of genome instability. Thus, most repetitive elements are usually meth…
Obesogen effect of bisphenol S alters mRNA expression and DNA methylation profiling in male mouse liver
2020
International audience; Environmental pollution is increasingly considered an important factor involved in the obesity incidence. Endocrine disruptors (EDs) are important actors in the concept of DOHaD (Developmental Origins of Health and Disease), where epigenetic mechanisms play crucial roles. Bisphenol A (BPA), a monomer used in the manufacture of plastics and resins is one of the most studied obesogenic endocrine disruptor. Bisphenol S (BPS), a BPA substitute, has the same obesogenic properties, acting at low doses with a sex-specific effect following perinatal exposure. Since the liver is a major organ in regulating body lipid homeostasis, we investigated gene expression and DNA methyl…
Histone Variant MacroH2A1 Marks Liver Aging and Orchestrates the Escape from Senescence Induced by DNA Hypomethylation in Hepatocellular Carcinoma
2015
The epigenetic basis of age-associated progression of liver diseases towards hepatocellular carcinoma (HCC) is unclear. MacroH2A1 is a variant of histone H2A1, present in the two isoforms, with fundamental roles in cell homeostasis. MacroH2A1 is a marker of senescence associated heterochromatic foci (SAHF) and synergizes with DNA demethylating chemotherapic agent 5-aza-2'-deoxycytidine (5-aza-dC) in silencing tumor suppressor genes in human fibroblasts. We show that protein levels of macroH2A1 isoforms are increased in the livers of old rodents and humans, and in human HCC tissue. Human HCC cells overexpressing macroH2A1 escape a 5-aza-dC-induced senescent phenotype, as determined by cell p…