• Lauren J Buro-Auriemma, Jacqueline Salit, Neil R Hackett, Matthew S Walters, Yael Strulovici-Barel, Michelle R Staudt, Jennifer Fuller, Mai Mahmoud, Christopher S Stevenson, Holly Hilton, Melisa W Y Ho, and Ronald G Crystal.
• Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA.
• Hum. Mol. Genet. 2013 Dec 1; 22 (23): 4726-38.

AbstractThe 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.

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