Abstract
BackgroundRepetitive elements take up >40% of the human genome and can change distribution through transposition, thus generating subfamilies. Repetitive element DNA methylation has associated with several diseases and environmental exposures, including exposure to airborne pollutants. No systematic analysis has yet been conducted to examine the effects of exposures across different repetitive element subfamilies. The purpose of the study is to evaluate sensitivity of DNA methylation in differentially‒evolved LINE, Alu, and HERV subfamilies to different types of airborne pollutants.MethodsWe sampled a total of 120 male participants from three studies (20 high-, 20 low-exposure in each study) of steel workers exposed to metal-rich particulate matter (measured as PM10) (Study 1); gas-station attendants exposed to air benzene (Study 2); and truck drivers exposed to traffic-derived elemental carbon (Study 3). We measured methylation by bisulfite-PCR-pyrosequencing in 10 differentially‒evolved repetitive element subfamilies.ResultsHigh-exposure groups exhibited subfamily-specific methylation differences compared to low-exposure groups: L1PA2 showed lower DNA methylation in steel workers (P=0.04) and gas station attendants (P=0.03); L1Ta showed lower DNA methylation in steel workers (P=0.02); AluYb8 showed higher DNA methylation in truck drivers (P=0.05). Within each study, dose–response analyses showed subfamily-specific correlations of methylation with exposure levels. Interaction models showed that the effects of the exposures on DNA methylation were dependent on the subfamily evolutionary age, with stronger effects on older LINEs from PM10 (p‒interaction=0.003) and benzene (p‒interaction=0.04), and on younger Alus from PM10 (p-interaction=0.02).ConclusionsThe evolutionary age of repetitive element subfamilies determines differential susceptibility of DNA methylation to airborne pollutants.
Highlights
Repetitive elements take up >40% of the human genome and can change distribution through transposition, generating subfamilies
DNA methylation of repetitive element subfamilies by exposure group We first examined DNA methylation in repetitive element subfamilies by contrasting the high- vs. low-exposure groups in analysis adjusted for age and smoking
L1Ta, the youngest of the LINE-1 showed in Study 1 significantly lower DNA methylation in steel workers with high exposure to metal-rich PM10 compared to the low-exposed controls (Figure 1D and see Evolutionary age (Mya)a
Summary
Repetitive elements take up >40% of the human genome and can change distribution through transposition, generating subfamilies. Repetitive element DNA methylation has associated with several diseases and environmental exposures, including exposure to airborne pollutants. Repetitive elements, L1s, are DNA sequences that only encode for proteins instrumental to their replication and insertion into new locations within the genome. Repetitive elements are believed to have reshaped the human genome through continuous jumping to remote genomic locations and through the activation of alternative transcription of nearby genes [4,5,6,7]. Many newly inserted repetitive elements have been observed in somatic tissues and, albeit non heritable, have been linked with human disease and cancers [8,9]
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