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Epigenetics was originally defined as the interaction of genes with their environment that brings the phenotype into being. It now refers to the study of heritable changes in gene expression that occur without a change in DNA sequence. To date, the best understood epigenetic mechanisms are CpG DNA methylation and histone modifications. DNA methylation in particular has been the subject of intense interest because of its recently recognized role in disease, as well as in the development and normal function of organisms. Much of the focus of disease-related research has been on cancer because of the recognition that epigenetic alterations are common in cancer and probably cooperate with genetic alterations to drive cancer formation. Our understanding of epigenetic mechanisms in controlling gene expression has resulted from the study of cell line systems and simple model systems, such as Arabidopsis thaliana. We are now moving into an era of more complex model systems, such as transgenic and knockout mouse models, which will lead to further insight into epigenetics in development and human disease. The current models have revealed complex, tissue-specific effects of epigenetic mechanisms and have further informed our understanding of the role of DNA methylation and histone modifications on disease and development. The current state of these models is the subject of this Commentary.

Insights into the role of DNA methylation in disease through the use of mouse models