Epigenetic mechanisms and the development of asthma

• Ivana V. Yang, PhD
, 
• David A. Schwartz, MD

Department of Medicine, University of Colorado School of Medicine, Aurora, Colo

Received 19 June 2012; received in revised form 26 July 2012; accepted 27 July 2012. published online 01 October 2012.

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Article Outline

• Abstract
• Epigenetic mechanisms
• Epigenomic study design
• Epigenomic profiling
• Epigenomic data analysis
• Epigenetic marks and the immune system
• Role of the environment and in utero exposures in modulating the epigenome
• Asthma epigenetics: Animal studies
• Asthma epigenetics: Human studies
• Challenges in understanding the asthma epigenome
• Potential effect of epigenetics research on asthma
• References
• Copyright

Asthma is heritable, influenced by the environment, and modified by in utero exposures and aging; all of these features are also common to epigenetic regulation. Furthermore, the transcription factors that are involved in the development of mature T cells that are critical to the T_H2 immune phenotype in asthmatic patients are regulated by epigenetic mechanisms. Epigenetic marks (DNA methylation, modifications of histone tails, and noncoding RNAs) work in concert with other components of the cellular regulatory machinery to control the spatial and temporal levels of expressed genes. Technology to measure epigenetic marks on a genomic scale and comprehensive approaches to data analysis have recently emerged and continue to improve. Alterations in epigenetic marks have been associated with exposures relevant to asthma, particularly air pollution and tobacco smoke, as well as asthma phenotypes, in a few population-based studies. On the other hand, animal studies have begun to decipher the role of epigenetic regulation of gene expression associated with the development of allergic airway disease. Epigenetic mechanisms represent a promising line of inquiry that might, in part, explain the inheritance and immunobiology of asthma.

Key words: Asthma, atopy, epigenetics, gene expression, DNA methylation, histone marks, noncoding RNAs

Abbreviations used: AHR, Airway hyperresponsiveness, CHARM, Comprehensive Analysis of Relative DNA Methylation, ChIP, Chromatin immunoprecipitation, DMR, Differentially methylated region, DNMT, DNA methyltransferase, Feno, Fraction of exhaled nitric oxide, FOXP3,Forkhead box protein 3, LCR, Locus control region, miRNA, MicroRNA, PM_2.5, Particulate matter of 2.5 μm in diameter or less, QTL,Quantitative trait locus, T-bet, T-box transcription factor, Treg, Regulatory T