Asthma is heritable, influenced by the environment, and is modified by in utero exposures and aging; all of these features are also common to epigenetic regulation. Furthermore, genetic variants that have been identified to date explain a small portion of asthma heritability. Finally, the transcription factors that are involved in the development of mature T cells that are critical to the Th2 immune phenotype in asthma are regulated by epigenetic mechanisms. Our group was the first to demonstrate a causal relationship between DNA methylation marks and both Th2 immunity and allergic airway disease in mice. We have also shown that DNA methylation marks in Th2 immune genes are associated with asthma and gene expression changes in peripheral blood mononuclear cells (PBMCs) from children in the inner city. We have also found pronounced changes in DNA methylation and gene expression in nasal epithelia of allergic asthmatics, suggesting that genes previously identified as important in the asthmatic airway epithelium appear to be epigenetically regulated. Our findings that epigenetic marks in immune cells and respiratory epithelia are associated with allergic asthma provide new targets for understanding the biology of the disease, developing biomarkers of exposure or disease, and potentially identifying novel therapeutic approaches for this disease. Learning Objectives 1. Discuss how epigenetic marks are influenced by the environment and are important in T cell lineage differentiation 2. Explain the association of epigenetic marks with asthma and disease subtypes