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

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, Ronald Crystal

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Abstract

The small airway epithelium (SAE), the first site of smoking-induced lung pathology, exhibits genome-wide changes in geneexpression in response to cigarettesmoking.Basedonthe 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 inSAEDNAmethylation 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 withnonsmokers, with67%of the regions with differentialmethylation occurring within 2 kbof 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.

Original languageEnglish
Article numberddt326
Pages (from-to)4726-4738
Number of pages13
JournalHuman Molecular Genetics
Volume22
Issue number23
DOIs
Publication statusPublished - 1 Dec 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Buro-Auriemma, L. J., Salit, J., Hackett, N. R., Walters, M. S., Strulovici-Barel, Y., Staudt, M. R., Fuller, J., Mahmoud, M., Stevenson, C. S., Hilton, H., Ho, M. W. Y., & Crystal, R. (2013). Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression. Human Molecular Genetics, 22(23), 4726-4738. [ddt326]. https://doi.org/10.1093/hmg/ddt326