Search results for "Epigenetics"

Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning

2012

Alcohol drinking during adolescence can induce long-lasting effects on the motivation to consume alcohol. Abnormal plasticity in reward-related processes might contribute to the vulnerability of adolescents to drug addiction. We have shown that binge-like ethanol treatment in adolescent rats induces alterations in the dopaminergic system and causes histone modifications in brain reward regions. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced alterations in gene expression and behavior, we addressed the hypothesis that ethanol is capable of inducing transcriptional changes by histone modifications in specific gene promoters in adolescen…

DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non-Atopic Asthma

2019

A high body mass (BMI) index has repeatedly been associated with non-atopic asthma, but the biological mechanism linking obesity to asthma is still poorly understood. We aimed to test the hypothesis that inflammation and/or innate immunity plays a role in the obesity-asthma link. DNA methylome was measured in blood samples of 61 non-atopic participants with asthma and 146 non-atopic participants without asthma (non-smokers for at least 10 years) taking part in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) study. Modification by DNA methylation of the association of BMI or BMI change over 10 years with adult-onset asthma was examined at each CpG sit…

Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs

2019

There is a growing body of evidence linking maternal overnutri-tion to obesity and psychopathology that can be conserved acrossmultiple generations. Recently, we demonstrated in a maternalhigh-fat diet (HFD; MHFD) mouse model that MHFD inducedenhanced hedonic behaviors and obesogenic phenotypes thatwere conserved across three generations via the paternal lineage,which was independent of sperm methylome changes. Here, weshow that sperm tRNA-derived small RNAs (tsRNAs) partly contrib-ute to the transmission of such phenotypes. We observe increasedexpression of sperm tsRNAs in the F1 male offspring born to HFD-exposed dams. Microinjection of sperm tsRNAs from the F1-HFDmale into normal zygotes…

Roles of the Core Components of the Mammalian miRISC in Chromatin Biology

2022

The Argonaute (AGO) and the Trinucleotide Repeat Containing 6 (TNRC6) family proteins are the core components of the mammalian microRNA-induced silencing complex (miRISC), the machinery that mediates microRNA function in the cytoplasm. The cytoplasmic miRISC-mediated post-transcriptional gene repression has been established as the canonical mechanism through which AGO and TNRC6 proteins operate. However, growing evidence points towards an additional mechanism through which AGO and TNRC6 regulate gene expression in the nucleus. While several mechanisms through which miRISC components function in the nucleus have been described, in this review we aim to summarize the major findings that have …

Relationship between endocrine disruptors and obesity with a focus on bisphenol A: a narrative review

2021

International audience; Introduction: Scientific data suggest that early exposure to endocrine-disrupting chemicals (EDCs) affect -repro, -neuro, -metabolic systems, to which are added other notions such as mixtures, window and duration of exposure, trans-generational effects, and epigenetic mechanisms. Methods: In the present narrative review, we studied the relationship between exposure to EDCs with the appearance and development of obesity. Results: Exposure to EDCs like Bisphenol A during the early stages of development has been shown to lead to weight gain and obesity. EDCs can interfere with endocrine signaling, affect adipocytes differentiation and endocrine function and disrupt meta…

EP569 Potential role of PAI-1 in endometrial cancer progression and its regulation by epigenetic mechanisms

2019

Introduction/Background Endometrial cancer (EC) is the most prevalent gyneacological cancer. It presents two subtypes, (Type-1 and Type-2), being the lately associated to worse prognosis and increased epithelial-to-mesenchymal transition (EMT). A growing evidence supports that uPA and PAI-1 play a role in solid tumour progression, though the exact role of PAI-1 and its epigenetic regulation in EC has not been completely established yet. Methodology 67 patients with EC and 36 control women were included. 5 miRNAs targeting PAI-1 mRNA (namely miR-99a-5p, miR-143-3p, miR-145-5p, miR-196b-5p y miR-301a-3p) were selected from miRNA expression profiles (Affymetrix, GeneChipmiRNA 2.0) and validate…

Metabolic memory in diabetic foot syndrome (dfs): epigenetic changes of the expression of micro-rnas and single nucleotide polymorphisms (snps) frequ…

2023

Background: Diabetic foot is a significant cause of morbidity in diabetic patients, with a rate that is approximatelytwice that of patients without foot ulcers. “Metabolic memory” represents the epigenetic changes induced by chronic hyperglycaemia, despite the correction of the glucose levels themselves. These epigenetic modifications appear to perpetuate the damage caused by persistently elevated glucose levels even in their absence, acting at various levels, mostly affecting the molecular processes of diabetic ulcer healing. Methods: The aim of our cross-sectional study was to analyse a cohort of patients with diabetes with and without lower limb ulcers. We examined the effects of epigene…

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…

Role of Microbiota in development, gene expression and epigenetic modifications in D. melanogaster host model

Eukaryotes and prokaryotes have developed mutually beneficial relationships over millennia of evolutionary adaptation. Recent observations suggest a strong correlation between the presence of Microbiota and host homeostasis, but little is known about the mechanisms they use to shape the physiology and to reprogram gene expression of their host. Using both conventionally reared and germ-free D. melanogaster as a model system, I found a role of bacteria in host protein expression and development, as germ-free flies develop more slowly than their conventional counterpart. Remarkably, using the classic variegated In(1)wm4 inversion, I identified a role of Microbiota as modifier of white Positio…

Photoinduced intersystem crossing in DNA oxidative lesions and epigenetic intermediates

2020

[EN] The propensity of 5-formyluracil and 5-formylcytosine, i.e. oxidative lesions and epigenetic intermediates, in acting as intrinsic DNA photosensitizers is unraveled by using a combination of molecular modeling, simulation and spectroscopy. Exploration of potential energy surfaces and non-adiabatic dynamics confirm a higher intersystem crossing rate for 5-formyluracil, whereas the kinetic models evidence different equilibria in the excited states for both compounds.