Journal
ENVIRONMENTAL EPIGENETICS
Volume 4, Issue 3, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eep/dvy020
Keywords
5-hydroxy-methylcytosine; 5-methyl-cytosine; TET1; traffic-related air pollution; allergen; airway epithelial cells
Categories
Funding
- NIH/NIAID [R21AI119236]
- ALA/AAAAI Respiratory Diseases Research Award [515708]
- NIH [R21 HG008186, R01 NS099068-01A1]
- Cincinnati Children's Hospital Center for Pediatric Genomics pilot study award
- Cincinnati Children's Hospital Research Fund Endowed Scholar award
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Exposures to diesel exhaust particles (DEP) from traffic and house dust mite (HDM) allergens significantly increase risks of airway diseases, including asthma. This negative impact of DEP and HDM may in part be mediated by epigenetic mechanisms. Beyond functioning as a mechanical barrier, airway epithelial cells provide the first line of immune defense towards DEP and HDM exposures. To understand the epigenetic responses of airway epithelial cells to these exposures, we exposed human bronchial epithelial cells to DEP and HDM and studied genome-wide 5-methyl-cytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) at base resolution. We found that exposures to DEP and HDM result in elevated TET1 and DNMT1 expression, associated with 5mC and 5hmC changes. Interestingly, over 20% of CpG sites are responsive to both exposures and changes in 5mC at these sites negatively correlated with gene expression differences. These 5mC and 5hmC changes are located in genes and pathways related to oxidative stress responses, epithelial function and immune cell responses and are enriched for binding sites of transcription factors (TFs) involved in these pathways. Histone marks associated with promoters, enhancers and actively transcribed gene bodies were associated with exposure-induced DNA methylation changes. Collectively, our data suggest that exposures to DEP and HDM alter 5mC and 5hmC levels at regulatory regions bound by TFs, which coordinate with histone marks to regulate gene networks of oxidative stress responses, epithelial function and immune cell responses. These observations provide novel insights into the epigenetic mechanisms that mediate the epithelial responses to DEP and HDM in airways.
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