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Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression.


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.

SUBMITTER: Buro-Auriemma LJ 

PROVIDER: S-EPMC3888123 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression.

Buro-Auriemma Lauren J LJ   Salit Jacqueline J   Hackett Neil R NR   Walters Matthew S MS   Strulovici-Barel Yael Y   Staudt Michelle R MR   Fuller Jennifer J   Mahmoud Mai M   Stevenson Christopher S CS   Hilton Holly H   Ho Melisa W Y MW   Crystal Ronald G RG  

Human molecular genetics 20130710 23


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 an  ...[more]

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