title: Hydroxymethylation as a Novel Environmental Biosensor.
abstract: 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. And 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.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.
authors.forename: T
authors.initials: T
authors.lastname: Dao
authors.affiliation: Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: R Y S
authors.initials: RY
authors.lastname: Cheng
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah, United States.
authors.forename: M P
authors.initials: MP
authors.lastname: Revelo
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.
authors.forename: W
authors.initials: W
authors.lastname: Mitzner
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.
authors.forename: Wy
authors.initials: W
authors.lastname: Tang
keywords: 5-carboxylmethylcytosine; 5-formylmethylcytosine; 5-hydroxymethylcytosine; 5-methylcytosine; DNA hydroxymethylation; DNA methylation; base excision repair; deamination; demethylation; environmental biosensor; environmental health; epigenetics; glucosylation; oxidation; ten-eleven translocation proteins