Hydroxymethylation as a Novel Environmental Biosensor

Beyond the genome, epigenetics has become a promising approach in understanding the interactions between the gene and the environment. Epigenetic regulation includes DNA methylation, histone modifications, and non-coding RNAs. Among these, DNA methylation, which is the addition of a methyl group to the fifth base of cytosine to produce 5-methylcytosine (5-mC), is most commonly studied. Epigenetic regulation has changed given the discovery of 5-hydroxymethylcytosine (5-hmC), considered the “sixth base,” and the nature of TET proteins to catalyze 5-mC oxidation to 5-hmC. 5-Hydroxymethylation has been proposed to be a stable intermediate between methylation and demethylation and has raised questions about the functions of 5-hmC in gene regulation in cells, tissues, and organs in response to environmental exposure. Herein, we have provided an introduction to the chemistry of 5-hydroxymethylation and the techniques for detection of 5-hydroxymethylation. In addition, we have reviewed current reports describing how 5-hmC responds to environmental factors, leading to the development of disease. Finally, we have discussed the potential use of 5-hmC in the study of disease development. All in all, it is our goal to provide innovative and convincing epigenetic studies for understanding the etiology of environmentally related human disease and translate these epigenetic findings into lifestyle recommendations and clinical practices to prevent and cure disease.