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