Perinatal lead (Pb) exposure results in sex and tissue-dependent adult DNA methylation alterations in murine IAP transposons.

Epidemiological and animal data suggest that adult chronic disease is influenced by early-life exposure-induced changes to the epigenome. Previously, we observed that perinatal lead (Pb) exposure results in persistent murine metabolic- and activity-related effects. Using phylogenetic and DNA methylation analysis, we have also identified novel intracisternal A particle (IAP) retrotransposons exhibiting regions of variable methylation as candidate loci for environmental effects on the epigenome. Here, we now evaluate brain and kidney DNA methylation profiles of four representative IAPs in adult mice exposed to human physiologically relevant levels of Pb two weeks prior to mating through lactation. When IAPs across the genome were evaluated globally, average (sd) methylation levels were 92.84% (3.74) differing by tissue (P < 0.001), but not sex or dose. By contrast, the four individual IAPs displayed tissue-specific Pb and sex effects. Medium Pb-exposed mice had 3.86% less brain methylation at IAP 110 (P < 0.01), while high Pb-exposed mice had 2.83% less brain methylation at IAP 236 (P = 0.01) and 1.77% less at IAP 506 (P = 0.05). Individual IAP DNA methylation differed by sex for IAP 110 in the brain and kidney, IAP 236 in the kidney, and IAP 1259 in the kidney. Using Tomtom, we identified three binding motifs that matched to each of our novel IAPs impacted by Pb, one of which (HMGA2) has been linked to metabolic-related conditions in both mice and humans. Thus, these recently identified IAPs display tissue-specific environmental lability as well as sex-specific differences supporting an epigenetic link between early exposure to Pb and later-in-life health outcomes. Environ. Mol. Mutagen. 58:540-550, 2017. © 2017 Wiley Periodicals, Inc.

Dietary intake is associated with respiratory health outcomes and DNA methylation in children with asthma.

BACKGROUND: Asthma is an increasingly common chronic disease among children, and data point toward a complex mechanism involving genetic, environmental and epigenetic factors. Epigenetic modifications such as DNA hypo- or hyper-methylation have been shown to occur in response to environmental exposures including dietary nutrients. METHODS: Within the context of the asthma randomized trial of indoor wood smoke (ARTIS) study, we investigated relationships between diet, asthma health measures, and DNA methylation. Asthma health measures included a quality of life instrument, diurnal peak flow variability (dPFV) and forced expiratory volume in the first second (FEV1). Dietary intake was assessed with a food frequency questionnaire. Methylation levels of LINE-1 repetitive element and two promoter CpG sites for interferon gamma (IFNγ, -186 and -54) from buccal cell DNA were measured using pyrosequencing assays. RESULTS: Data were collected on 32 children with asthma living in western Montana who were recruited to the ARTIS study. Selenium and several methyl donor dietary nutrients were positively associated with the asthma quality of life measure. Intake of methyl donating nutrients including folate was positively associated LINE-1 methylation and negatively associated with IFNγ CpG-186. Higher levels of LINE-1 methylation were associated with greater dPFV. CONCLUSION: We identified several nutrients that were associated with improved quality of life measures among children with asthma. The IFNγ promoter CpG site -186 but not -54 was associated with the intake of selected dietary nutrients. However, in this small population of children with asthma, the IFNγ promoter CpG sites were not associated with respiratory health measures so it remains unclear through which epigenetic mechanism these nutrients are impacting the quality of life measure. These findings add to the evidence that dietary nutrients, particularly foods containing methyl donors, may be important for epigenetic regulation as it pertains to the control of asthma. Trial registration ClincialTrials.gov NCT00807183. Registered 10 December 2008.