title: 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.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Buro-Auriemma
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Salit
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Walters
authors.forename: Yael
authors.initials: Y
authors.lastname: Strulovici-Barel
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Staudt
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fuller
authors.forename: Mai
authors.initials: M
authors.lastname: Mahmoud
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Stevenson
authors.forename: Holly
authors.initials: H
authors.lastname: Hilton
authors.forename: Melisa W Y
authors.initials: MW
authors.lastname: Ho
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics* / Q000378:metabolism; D024363:Transcription Initiation Site; D055815:Young Adult