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1.
Melatonin and Vitamin D Orchestrate Adipose Derived Stem Cell Fate by Modulating Epigenetic Regulatory Genes.
Santaniello, S, Cruciani, S, Basoli, V, Balzano, F, Bellu, E, Garroni, G, Ginesu, GC, Cossu, ML, Facchin, F, Delitala, AP, et al
International journal of medical sciences. 2018;(14):1631-1639
Abstract
Melatonin, that regulates many physiological processes including circadian rhythms, is a molecule able to promote osteoblasts maturation in vitro and to prevent bone loss in vivo, while regulating also adipocytes metabolism. In this regard, we have previously shown that melatonin in combination with vitamin D, is able to counteract the appearance of an adipogenic phenotype in adipose derived stem cells (ADSCs), cultured in an adipogenic favoring condition. In the present study, we aimed at evaluating the specific phenotype elicited by melatonin and vitamin D based medium, considering also the involvement of epigenetic regulating genes. ADSCs were cultured in a specific adipogenic conditioned media, in the presence of melatonin alone or with vitamin D. The expression of specific osteogenic related genes was evaluated at different time points, together with the histone deacetylases epigenetic regulators, HDAC1 and Sirtuins (SIRT) 1 and 2. Our results show that melatonin and vitamin D are able to modulate ADSCs commitment towards osteogenic phenotype through the upregulation of HDAC1, SIRT 1 and 2, unfolding an epigenetic regulation in stem cell differentiation and opening novel strategies for future therapeutic balancing of stem cell fate toward adipogenic or osteogenic phenotype.
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2.
Epigenetic changes due to physical activity.
Rezapour, S, Shiravand, M, Mardani, M
Biotechnology and applied biochemistry. 2018;(6):761-767
Abstract
One of the epigenetic-modifying factors is regular and continuous physical activity. This article attempts to investigate the effects of physical activity and exercise on changes in histone proteins and gene expression, as well as the effect of these exercises on the prevention of certain cancers and the ejection of age-related illnesses and cellular oxidation interactions. All of this is due to epigenetic changes and gene expression. Most studies have reported the positive effects of regular exercises on the expression of histone proteins. DNA methylation and the prevention of certain diseases such as cancer and respiratory diseases, caused by antioxidative interactions that occur more often in the elderly, have been studied.
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3.
ZBTB24 is a transcriptional regulator that coordinates with DNMT3B to control DNA methylation.
Thompson, JJ, Kaur, R, Sosa, CP, Lee, JH, Kashiwagi, K, Zhou, D, Robertson, KD
Nucleic acids research. 2018;(19):10034-10051
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Abstract
The interplay between transcription factors and epigenetic writers like the DNA methyltransferases (DNMTs), and the role of this interplay in gene expression, is being increasingly appreciated. ZBTB24, a poorly characterized zinc-finger protein, or the de novo methyltransferase DNMT3B, when mutated, cause Immunodeficiency, Centromere Instability, and Facial anomalies (ICF) syndrome, suggesting an underlying mechanistic link. Chromatin immunoprecipitation coupled with loss-of-function approaches in model systems revealed common loci bound by ZBTB24 and DNMT3B, where they function to regulate gene body methylation. Genes coordinately regulated by ZBTB24 and DNMT3B are enriched for molecular mechanisms essential for cellular homeostasis, highlighting the importance of the ZBTB24-DNMT3B interplay in maintaining epigenetic patterns required for normal cellular function. We identify a ZBTB24 DNA binding motif, which is contained within the promoters of most of its transcriptional targets, including CDCA7, AXIN2, and OSTC. Direct binding of ZBTB24 at the promoters of these genes targets them for transcriptional activation. ZBTB24 binding at the promoters of RNF169 and CAMKMT, however, targets them for transcriptional repression. The involvement of ZBTB24 targets in diverse cellular programs, including the VDR/RXR and interferon regulatory pathways, suggest that ZBTB24's role as a transcriptional regulator is not restricted to immune cells.
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Centenarians as a model to discover genetic and epigenetic signatures of healthy ageing.
Puca, AA, Spinelli, C, Accardi, G, Villa, F, Caruso, C
Mechanisms of ageing and development. 2018;:95-102
Abstract
Centenarians are a model of successful ageing. The data favours the theory that, in order to live to 100, it is mandatory to inherit the right genetic variants from parents or acquire epigenetic variants through the environment. Therefore, the study of epigenetic signatures of healthy ageing is becoming an important aspect to identify the role of chromatin modification in ageing and understand how manage this fine-tuning system. So, according to the concept of developmental plasticity, establishment of a longevity phenotype requires a combination of stochastic and non-stochastic events that modulate the genetic substrate and leads to a different outcome. It can be concluded that centenarians have a more powerful "engine" shaped by evolution, and that the environment, through epigenetic system, is a component influencing outcome.
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Galactose-1-phosphate uridyltransferase deficiency: A literature review of the putative mechanisms of short and long-term complications and allelic variants.
Viggiano, E, Marabotti, A, Politano, L, Burlina, A
Clinical genetics. 2018;(2):206-215
Abstract
Galactosemia type 1 is an autosomal recessive disorder of galactose metabolism, determined by a deficiency in the enzyme galactose-1-phosphate uridyltransferase (GALT). GALT deficiency is classified as severe or variant depending on biochemical phenotype, genotype and potential to develop acute and long-term complications. Neonatal symptoms usually resolve after galactose-restricted diet; however, some patients, despite the diet, can develop long-term complications, in particular when the GALT enzyme activity results absent or severely decreased. The mechanisms of acute and long-term complications are still discussed and several hypotheses are presented in the literature like enzymatic inhibition, osmotic stress, endoplasmic reticulum stress, oxidative stress, defects of glycosylation or epigenetic modification. This review summarizes the current knowledge of galactosemia, in particular the putative mechanisms of neonatal and long-term complications and the molecular genetics of GALT deficiency.
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Exploratory analysis of the human breast DNA methylation profile upon soymilk exposure.
Coussement, L, Bolca, S, Van Criekinge, W, Trooskens, G, Mensaert, K, Poels, K, Roche, N, Blondeel, P, Godderis, L, Depypere, H, et al
Scientific reports. 2018;(1):13617
Abstract
Upon soy consumption, isoflavone metabolites attain bioactive concentrations in breast tissue possibly affecting health. Though in vitro epigenetic activity of soy metabolites has been described, the in vivo impact on the epigenome is largely unknown. Therefore, in this case-control study, the breast glandular tissue DNA methylome was explored in women undergoing an aesthetic breast reduction. After a run-in phase, 10 generally healthy Belgian or Dutch women received soymilk for 5 days. MethylCap-seq methylation profiles were compared with those of 10 matched controls. Isoflavones and their microbial metabolites were quantified in urine, serum, and glandular breast tissue (liquid chromatography-mass spectrometry) and 17β-estradiol in glandular breast tissue (immunoassay). Global DNA methylation levels were obtained for 6 cases and 5 controls using liquid chromatography-mass spectrometry. Although lower MethylCap-seq coverages were observed, mass spectrometry results and computational LINE-1 methylation analysis did not provide evidence supporting global methylation alterations upon treatment. At a false discovery rate of 0.05, no differentially methylated loci were identified. Moreover, a set of previously identified loci was specifically tested, but earlier reported results could not be validated. In conclusion, after a 5-day soymilk treatment, no major general epigenetic reprogramming in breast tissue could be found in this exploratory study.
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7.
Insights on the epigenetic mechanisms underlying pulmonary arterial hypertension.
Luna, RCP, de Oliveira, Y, Lisboa, JVC, Chaves, TR, de Araújo, TAM, de Sousa, EE, Miranda Neto, M, Pirola, L, Braga, VA, de Brito Alves, JL
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2018;(12):e7437
Abstract
Pulmonary arterial hypertension (PAH), characterized by localized increased arterial blood pressure in the lungs, is a slow developing long-term disease that can be fatal. PAH is characterized by inflammation, vascular tone imbalance, pathological pulmonary vascular remodeling, and right-sided heart failure. Current treatments for PAH are palliative and development of new therapies is necessary. Recent and relevant studies have demonstrated that epigenetic processes may exert key influences on the pathogenesis of PAH and may be promising therapeutic targets in the prevention and/or cure of this condition. The aim of the present mini-review is to summarize the occurrence of epigenetic-based mechanisms in the context of PAH physiopathology, focusing on the roles of DNA methylation, histone post-translational modifications and non-coding RNAs. We also discuss the potential of epigenetic-based therapies for PAH.
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8.
Epigenetic changes and their implications in autoimmune hepatitis.
Czaja, AJ
European journal of clinical investigation. 2018;(4)
Abstract
BACKGROUND The genetic risk of autoimmune hepatitis is insufficient to explain the observed risk, and epigenetic changes may explain disparities in disease occurrence in different populations within and between countries. The goal of this review was to examine how epigenetic changes induced by the environment or inherited as a phenotypic trait may affect autoimmune hepatitis and be amenable to therapeutic intervention. MATERIALS AND METHODS Pertinent abstracts were identified in PubMed by multiple search terms. The number of abstracts reviewed was 1689, and the number of full-length articles reviewed exceeded 150. RESULTS Activation of pro-inflammatory genes in autoimmune disease is associated with hypomethylation of deoxyribonucleic acid and modification of histones within chromatin. Organ-specific microribonucleic acids can silence genes by marking messenger ribonucleic acids for degradation, and they can promote inflammatory activity or immunosuppression. High circulating levels of the microribonucleic acids 21 and 122 have been demonstrated in autoimmune hepatitis, and they may increase production of pro-inflammatory cytokines. Microribonucleic acids are also essential for maintaining regulatory T cells. Drugs, pollutants, infections, diet and ageing can induce inheritable epigenetic changes favouring autoimmunity. Reversal is feasible by manipulating enzymes, transcription factors, gene-silencing molecules and toxic exposures or by administering methyl donors and correcting vitamin D deficiency. Gene targets, site specificity, efficacy and consequences are uncertain. CONCLUSIONS Potentially reversible epigenetic changes may affect the occurrence and outcome of autoimmune hepatitis, and investigations are warranted to determine the nature of these changes, key genomic targets, and feasible interventions and their consequences.
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Effects of arsenic toxicity beyond epigenetic modifications.
Bjørklund, G, Aaseth, J, Chirumbolo, S, Urbina, MA, Uddin, R
Environmental geochemistry and health. 2018;(3):955-965
Abstract
Worldwide chronic arsenic (As) poisoning by arsenic-contaminated groundwater is one of the most threatening public health problems. Chronic inorganic As (inAs) exposure has been associated with various forms of cancers and numerous other pathological effects in humans, collectively known as arsenicosis. Over the past decade, evidence indicated that As-induced epigenetic modifications have a role in the adverse effects on human health. The main objective of this article is to review the evidence on epigenetic modifications induced by arsenicals. The epigenetic components play a crucial role in the regulation of gene expression, at both transcriptional and posttranscriptional levels. We synthesized the large body of existing research on arsenic exposure and epigenetic mechanisms of health outcomes with an emphasis on recent publications. Changes in patterns of DNA methylation, histone posttranslational modifications, and microRNAs have been repeatedly observed after inAs exposure in laboratory studies and in studies of human populations. Such alterations have the potential to disturb cellular homeostasis, resulting in the modulation of key pathways in the As-induced carcinogenesis. The present article reviews recent data on As-induced epigenetic effects and concludes that it is time for heightened awareness of pathogenic arsenic exposure, particularly for pregnant women and children, given the potential for a long-lasting disturbed cellular homeostasis.
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10.
[Epigenetics in age-related macular degeneration (AMD) - French translation of the article].
Desmettre, T
Journal francais d'ophtalmologie. 2018;(10):981-990
Abstract
Age-related macular degeneration (AMD) is a complex multifactorial condition involving multiple genetic, environmental and constitutional factors. Inflammation, oxidative stress and lipid metabolism seem to be the most important factors in the pathogenesis of the disease. The importance of genetic factors has mainly been revealed with the influence of histocompatibility complement factor H (CFH) variations and the ARSM2 susceptibility gene. Another component, epigenetics, could help to explain some of the relationships between environmental and genetic factors. Epigenetics is defined as the study of modulations of gene activity that can be transmitted over cell divisions without involving mutation of the DNA sequence. The molecules that are involved in these mechanisms are referred to as the epigenome. The mechanisms involve DNA methylation, histone modification, chromatin remodeling, and gene inhibition by non-coding RNA. Epigenetics could explain how the environment may induce relatively stable changes in traits or even diseases, possibly inheritable over several generations. Epigenetic traits established during development, and/or acquired under the influence of nutritional factors or other environmental factors, could influence the interactions between genes and the environment. Several authors have recently shown the influence of epigenetic factors in the pathogenesis of ocular diseases such as cataract, dry eye, glaucoma, diabetic retinopathy and more recently AMD. A better understanding of the involvement of genetic variants at risk, their relationship with epigenetics and environmental factors would certainly help to better assess the risk of developing AMD or better understand recent changes in the incidence of the disease.