Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression. Academic Article uri icon

Overview

MeSH

  • Adult
  • Case-Control Studies
  • DNA Methylation
  • Female
  • Gene Expression Profiling
  • Genome, Human
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Transcription Initiation Site
  • Young Adult

MeSH Major

  • 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.

publication date

  • December 1, 2013

has subject area

  • Adult
  • Case-Control Studies
  • DNA Methylation
  • Epigenesis, Genetic
  • Epithelium
  • Female
  • Gene Expression Profiling
  • Genome, Human
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Respiratory Mucosa
  • Smoking
  • Transcription Initiation Site
  • Young Adult

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3888123

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddt326

PubMed ID

  • 23842454

Additional Document Info

start page

  • 4726

end page

  • 4738

volume

  • 22

number

  • 23