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      Prenatal epigenetics diets play protective roles against environmental pollution

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          Abstract

          It is thought that germ cells and preimplantation embryos during development are most susceptible to endogenous and exogenous environmental factors because the epigenome in those cells is undergoing dramatic elimination and reconstruction. Exposure to environmental factors such as nutrition, climate, stress, pathogens, toxins, and even social behavior during gametogenesis and early embryogenesis has been shown to influence disease susceptibility in the offspring. Early-life epigenetic modifications, which determine the expression of genetic information stored in the genome, are viewed as one of the general mechanisms linking prenatal exposure and phenotypic changes later in life. From atmospheric pollution, endocrine-disrupting chemicals to heavy metals, research increasingly suggests that environmental pollutions have already produced significant consequences on human health. Moreover, mounting evidence now links such pollution to relevant modification in the epigenome. The epigenetics diet, referring to a class of bioactive dietary compounds such as isothiocyanates in broccoli, genistein in soybean, resveratrol in grape, epigallocatechin-3-gallate in green tea, and ascorbic acid in fruits, has been shown to modify the epigenome leading to beneficial health outcomes. This review will primarily focus on the causes and consequences of prenatal environment pollution exposure on the epigenome, and the potential protective role of the epigenetics diet, which could play a central role in neutralizing epigenomic aberrations against environmental pollutions.

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          Gene body methylation can alter gene expression and is a therapeutic target in cancer.

          DNA methylation in promoters is well known to silence genes and is the presumed therapeutic target of methylation inhibitors. Gene body methylation is positively correlated with expression, yet its function is unknown. We show that 5-aza-2'-deoxycytidine treatment not only reactivates genes but decreases the overexpression of genes, many of which are involved in metabolic processes regulated by c-MYC. Downregulation is caused by DNA demethylation of the gene bodies and restoration of high levels of expression requires remethylation by DNMT3B. Gene body methylation may, therefore, be an unexpected therapeutic target for DNA methylation inhibitors, resulting in the normalization of gene overexpression induced during carcinogenesis. Our results provide direct evidence for a causal relationship between gene body methylation and transcription. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Sirtuin activators mimic caloric restriction and delay ageing in metazoans.

            Caloric restriction extends lifespan in numerous species. In the budding yeast Saccharomyces cerevisiae this effect requires Sir2 (ref. 1), a member of the sirtuin family of NAD+-dependent deacetylases. Sirtuin activating compounds (STACs) can promote the survival of human cells and extend the replicative lifespan of yeast. Here we show that resveratrol and other STACs activate sirtuins from Caenorhabditis elegans and Drosophila melanogaster, and extend the lifespan of these animals without reducing fecundity. Lifespan extension is dependent on functional Sir2, and is not observed when nutrients are restricted. Together these data indicate that STACs slow metazoan ageing by mechanisms that may be related to caloric restriction.
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              Developmental plasticity and human health.

              Many plants and animals are capable of developing in a variety of ways, forming characteristics that are well adapted to the environments in which they are likely to live. In adverse circumstances, for example, small size and slow metabolism can facilitate survival, whereas larger size and more rapid metabolism have advantages for reproductive success when resources are more abundant. Often these characteristics are induced in early life or are even set by cues to which their parents or grandparents were exposed. Individuals developmentally adapted to one environment may, however, be at risk when exposed to another when they are older. The biological evidence may be relevant to the understanding of human development and susceptibility to disease. As the nutritional state of many human mothers has improved around the world, the characteristics of their offspring--such as body size and metabolism--have also changed. Responsiveness to their mothers' condition before birth may generally prepare individuals so that they are best suited to the environment forecast by cues available in early life. Paradoxically, however, rapid improvements in nutrition and other environmental conditions may have damaging effects on the health of those people whose parents and grandparents lived in impoverished conditions. A fuller understanding of patterns of human plasticity in response to early nutrition and other environmental factors will have implications for the administration of public health.
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                Author and article information

                Contributors
                lyy@uab.edu
                trygve@uab.edu
                Journal
                Clin Epigenetics
                Clin Epigenetics
                Clinical Epigenetics
                BioMed Central (London )
                1868-7075
                1868-7083
                16 May 2019
                16 May 2019
                2019
                : 11
                : 82
                Affiliations
                [1 ]ISNI 0000000106344187, GRID grid.265892.2, Department of Biology, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [2 ]ISNI 0000000106344187, GRID grid.265892.2, Department of Pharmacology and Toxicology, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [3 ]ISNI 0000000106344187, GRID grid.265892.2, Comprehensive Cancer Center, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [4 ]ISNI 0000000106344187, GRID grid.265892.2, Nutrition Obesity Research Center, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [5 ]ISNI 0000000106344187, GRID grid.265892.2, Comprehensive Center for Healthy Aging, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [6 ]ISNI 0000000106344187, GRID grid.265892.2, Comprehensive Diabetes Center, , University of Alabama at Birmingham, ; Birmingham, AL USA
                Author information
                http://orcid.org/0000-0002-0284-1511
                Article
                659
                10.1186/s13148-019-0659-4
                6524340
                31097039
                dfdd2cb2-705c-4c8a-ae93-08fc8352013e
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 7 February 2019
                : 27 March 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000054, National Cancer Institute;
                Award ID: R01CA178441
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01CA204346
                Funded by: FundRef http://dx.doi.org/10.13039/100008460, National Center for Complementary and Integrative Health;
                Award ID: K01AT009373
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
                Award ID: P30DK056336
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Genetics
                epigenetics diet,environmental pollution,dna methylation,histone modification,mirna
                Genetics
                epigenetics diet, environmental pollution, dna methylation, histone modification, mirna

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