title: Evolutionary age of repetitive element subfamilies and sensitivity of DNA methylation to airborne pollutants.
abstract: BACKGROUND
  Repetitive 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  High-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).
  
  
  CONCLUSIONS
  The evolutionary age of repetitive element subfamilies determines differential susceptibility of DNA methylation to airborne pollutants.
authors.affiliation: Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA, USA. hmbyun@hsph.harvard.edu
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.forename: Valeria
authors.initials: V
authors.lastname: Motta
authors.forename: Tommaso
authors.initials: T
authors.lastname: Panni
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D000397:Air Pollution; D001554:Benzene / Q000009:adverse effects; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D019143:Evolution, Molecular; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D052638:Particulate Matter / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D013232:Steel / Q000009:adverse effects; D001335:Vehicle Emissions / Q000633:toxicity
chemical_list: D000395:Air Pollutants, Occupational; D052638:Particulate Matter; D001335:Vehicle Emissions; D013232:Steel; D001554:Benzene