Environmental exposures and gene regulation in disease etiology

Edwards, Thea M.; Myers, John Peterson

doi:10.1590/s1413-81232008000100030

Cited by 46 publications

(32 citation statements)

References 98 publications

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“…AS has been shown to play fundamental roles in sex determination, development, behavior, and disease, and in worker honey bees, sterility, which is a hallmark of eusociality (1,34,35). Recently, DNA methylation has been detected in the genomes of other important social insects including several ants and termites (36,37) and has been implicated in caste differentiation and behavioral maturation (8,38).…”

Section: Resultsmentioning

confidence: 99%

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RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee

Li-Byarlay

Stroud

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

221

214

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Studies of DNA methylation from fungi, plants, and animals indicate that gene body methylation is ancient and highly conserved in eukaryotic genomes, but its role has not been clearly defined. It has been postulated that regulation of alternative splicing of transcripts was an original function of DNA methylation, but a direct experimental test of the effect of methylation on alternative slicing at the whole genome level has never been performed. To do this, we developed a unique method to administer RNA interference (RNAi) in a high-throughput and noninvasive manner and then used it to knock down the expression of DNA methyltransferase 3 (dnmt3), which is required for de novo DNA methylation. We chose the honey bee (Apis mellifera) for this test because it has recently emerged as an important model organism for studying the effects of DNA methylation on development and social behavior, and DNA methylation in honey bees is predominantly on gene bodies. Here we show that dnmt3 RNAi decreased global genomic methylation level as expected and in addition caused widespread and diverse changes in alternative splicing in fat tissue. Four different types of splicing events were affected by dnmt3 gene knockdown, and change in two types, exon skipping and intron retention, was directly related to decreased methylation. These results demonstrate that one function of gene body DNA methylation is to regulate alternative splicing.epigenetics | gene regulation | gene silencing | insect

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Section: Resultsmentioning

confidence: 99%

“…DNA cytosine methylation is an epigenetic mechanism that mediates many environmental influences on gene expression, affecting diverse aspects of organismal function and disease (1), and is one of the best studied mechanisms (2). DNA methylation of CG sites in the promoters of genes in plants and some species of animals acts to repress transcription (3).…”

mentioning

confidence: 99%

RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee

Li-Byarlay

Stroud

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

221

214

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“…reduced proportion of healthy ovarian follicles). There is evidence from rat studies that perturbations of components of the reproductive system induced in one generation by EDC exposure can be expressed at least up to the F4 generation, even in the absence of any further exposure (Anway & Skinner 2006;Crews et al 2007;Edwards & Myers 2007). Such transgenerational epigenetic effects of EDC exposure are yet to be demonstrated more widely and the extent to which they occur is likely to depend on the chemical, animal species and physiological system involved.…”

Section: Domestic Animal Studies: a Clue To The Threat To Wildlifementioning

confidence: 99%

Anthropogenic pollutants: a threat to ecosystem sustainability?

Rhind¹

2009

Phil. Trans. R. Soc. B

166

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Pollutants, including synthetic organic materials and heavy metals, are known to adversely affect physiological systems in all animal species studied to date. While many individual chemicals can perturb normal functions, the combined actions of multiple pollutants are of particular concern because they can exert effects even when each individual chemical is present at concentrations too low to be individually effective. The biological effects of pollutants differ greatly between species reflecting differences in the pattern of exposure, routes of uptake, metabolism following uptake, rates of accumulation and sensitivity of the target organs. Thus, understanding of the effects of pollutants on wildlife and ecosystems will require detailed study of many different species, representing a wide range of taxa. However, such studies can be informed by knowledge obtained in more controlled conditions which may indicate likely mechanisms of action and suitable endpoint measurements. Responses may be exacerbated by interactions between the effects of pollutants and environmental stressors, such as under-nutrition or osmotic stresses and so changes in such variables associated with climatic changes may exacerbate physiological responses to pollutant burdens.

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“…Regarding the multitude of chemicals present in the environment, fast and high-throughput methods are highly desirable for screening and characterization of their epigenetic toxicity [18]. Nuclear extract containing DNA methyltranferase activity has been exploited to evaluate the metal epigenotoxicity [19].…”

Section: Introductionmentioning

confidence: 99%

Epigenotoxicity of environmental pollutants evaluated by a combination of DNA methylation inhibition and capillary electrophoresis–laser-induced fluorescence immunoassay

Wang

2013

Anal Bioanal Chem

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A variety of environmental pollutants may cause abnormal DNA methylation, which further disturb gene expression. In this work, we developed a rapid and sensitive method for the characterization and identification of the epigenotoxicity of environmental pollutants in terms of DNA methylation. The method combines in vitro inhibition reactions of a model DNA methyltransferase (DNMT) with rapid and sensitive capillary electrophoresis-laser-induced fluorescence (CE-LIF) immunoassays. This method was first assessed using two known DNMT inhibitors, (-)-epigallocatechin-3-gallate and RG108, and then applied to epigenotoxic evaluation of four aldehydes and six benzo-1,4-quinones. It was found that all these electrophilic chemicals could inhibit DNMT activity, probably due to their interactions with the active sites of DNMT. Interestingly, benzo-1,4-quinones displayed more inhibitory effects on DNMT activity than aldehydes. Among the tested six benzo-1,4-quinones, halogenated benzo-1,4-quinone showed higher inhibitory activity than non-halogenated p-benzo-1,4-quinone. Owing to its speed and sensitivity, our method will be potentially applicable for fast epigenotoxic screening of environmental pollutants and mechanistic study of environmental epigenetics.

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Environmental exposures and gene regulation in disease etiology

Abstract: Health or disease is shaped for all individuals by interactions between their genes and

Cited by 46 publications

References 98 publications

RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee

RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee

Anthropogenic pollutants: a threat to ecosystem sustainability?

Epigenotoxicity of environmental pollutants evaluated by a combination of DNA methylation inhibition and capillary electrophoresis–laser-induced fluorescence immunoassay

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