Role of epigenetic mechanisms in the pathogenesis of chronic respiratory diseases and response to inhaled exposures: From basic concepts to clinical applications.

Abstract

Epigenetic modifications are chemical groups in our DNA (and chromatin) that determine which genes are active and which are shut off. Importantly, they integrate environmental signals to direct cellular function. Upon chronic environmental exposures, the epigenetic signature of lung cells gets altered, triggering aberrant gene expression programs that can lead to the development of chronic lung diseases. In addition to driving disease, epigenetic marks can serve as attractive lung disease biomarkers, due to early onset, disease specificity, and stability, warranting the need for more epigenetic research in the lung field. Despite substantial progress in mapping epigenetic alterations (mostly DNA methylation) in chronic lung diseases, the molecular mechanisms leading to their establishment are largely unknown. This review is meant as a guide for clinicians and lung researchers interested in epigenetic regulation with a focus on DNA methylation. It provides a short introduction to the main epigenetic mechanisms (DNA methylation, histone modifications and non-coding RNA) and the machinery responsible for their establishment and removal. It presents examples of epigenetic dysregulation across a spectrum of chronic lung diseases and discusses the current state of epigenetic therapies. Finally, it introduces the concept of epigenetic editing, an exciting novel approach to dissecting the functional role of epigenetic modifications. The promise of this emerging technology for the functional study of epigenetic mechanisms in cells and its potential future use in the clinic is further discussed.