Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression.
| Publication Type | Academic Article |
| Authors | Buro-Auriemma L, Salit J, Hackett N, Walters M, Strulovici-Barel Y, Staudt M, Fuller J, Mahmoud M, Stevenson C, Hilton H, Ho M, Crystal R |
| Journal | Hum Mol Genet |
| Volume | 22 |
| Issue | 23 |
| Pagination | 4726-38 |
| Date Published | 07/10/2013 |
| ISSN | 1460-2083 |
| Keywords | Epigenesis, Genetic, Epithelium, Respiratory Mucosa, Smoking |
| Abstract | The small airway epithelium (SAE), the first site of smoking-induced lung pathology, exhibits genome-wide changes in gene expression in response to cigarette smoking. Based on the increasing evidence that the epigenome can respond to external stimuli in a rapid manner, we assessed the SAE of smokers for genome-wide DNA methylation changes compared with nonsmokers, and whether changes in SAE DNA methylation were linked to the transcriptional output of these cells. Using genome-wide methylation analysis of SAE DNA of nonsmokers and smokers, the data identified 204 unique genes differentially methylated in SAE DNA of smokers compared with nonsmokers, with 67% of the regions with differential methylation occurring within 2 kb of the transcriptional start site. Among the genes with differential methylation were those related to metabolism, transcription, signal transduction and transport. For the differentially methylated genes, 35 exhibited a correlation with gene expression, 54% with an inverse correlation of DNA methylation with gene expression and 46% a direct correlation. These observations provide evidence that cigarette smoking alters the DNA methylation patterning of the SAE and that, for some genes, these changes are associated with the smoking-related changes in gene expression. |
| DOI | 10.1093/hmg/ddt326 |
| PubMed ID | 23842454 |
| PubMed Central ID | PMC3888123 |