Although obesity, reduced physical activity, and aging increase susceptibility to type 2 diabetes, many people exposed to these risk factors do not develop the disease. Recent genome-wide association studies have identified a number of genetic variants that explain some of the interindividual variation in diabetes susceptibility (1–5). There is also a growing body of literature suggesting a role for epigenetic factors in the complex interplay between genes and the environment. Nevertheless, our knowledge about the molecular mechanisms linking environmental factors and type 2 diabetes still remains limited. This perspective will provide some insights into epigenetic mechanisms associated with type 2 diabetes.
An overview of epigenetic regulation.
Although there is no uniform definition of epigenetics, it has been described as heritable changes in gene function that occur without a change in the nucleotide sequence (6). Epigenetic modifications can be passed from one cell generation to the next (mitotic inheritance) and between generations of a species (meiotic inheritance). In plants, it is well established that epigenetic modifications can be inherited from one generation to the next (7). However, there is only limited information about the inheritance of epigenetic traits between generations in animals (8,9). Notably, epigenetic effects may also be affected by the environment, making them potentially important pathogenic mechanisms in complex multifactorial diseases such as type 2 diabetes (Fig. 1). Epigenetic factors include DNA methylations, histone modifications, and microRNAs, and they can help to explain how cells with identical DNA can differentiate into different cell types with different phenotypes. This perspective will focus on the roles of DNA methylation and histone modification in the pathogenesis of type 2 diabetes.
Cytosine residues occurring in CG dinucleotides are targets for DNA methylation in vertebrates, and DNA methylation is associated with …