Epigenetic control of gene expression in the lung

Abstract

Epigenetics is traditionally defined as the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence. There are three main classes of epigenetic marks--DNA methylation, modifications of histone tails, and noncoding RNAs--each of which may be influenced by the environment, diet, diseases, and ageing. Importantly, epigenetic marks have been shown to influence immune cell maturation and are associated with the risk of developing various forms of cancer, including lung cancer. Moreover, there is emerging evidence that these epigenetic marks affect gene expression in the lung and are associated with benign lung diseases, such as asthma, chronic obstructive pulmonary disease, and interstitial lung disease. Technological advances have made it feasible to study epigenetic marks in the lung, and it is anticipated that this knowledge will enhance our understanding of the dynamic biology in the lung and lead to the development of novel diagnostic and therapeutic approaches for our patients with lung disease.

Figures

Figure 1.

(a) Epigenetic mechanisms in eukaryotes—DNA methylation, modifications of histone tails, and noncoding RNAs. (b) Effect of epigenetic marks on gene expression. Wide blue arrows indicate cross-talk between DNA methylation and histone modifications.

Figure 2.

Technologies for the assessment of epigenetic marks. Samples are prepared and the extent of epigenetic modification assessed using pyrosequencing for DNA methylation or quantitative PCR for histone modifications and miRNAs (single locus), epityper assays (1-40 loci, DNA methylation only), microarrays (a thousand to a few million loci; CHARM interogates 4.6M individual CpGs) or next-generation sequencing (entire genome). Epityper image used with permission from Sequenom (www.sequenom.com) and CHIP-seq image with permission from Life Technologies (www.lifetechnologies.com). Methyl-seq image reprinted from Bormann Chung PLoS One 2010;22:e9320 under open-access license.