AbstractBeyond 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. Epigenet-ic 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 environ-mental 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 un-derstanding the etiology of environmentally related human
disease and translate these epigenetic findings into
lifestyle recommendations and clinical practices to pre-vent and cure disease.
Keywords5-Hydroxymethylcytosine.5-Methylcytosine.
5-Formylmethylcytosine.5-Carboxylmethylcytosine.DNA
methylation.DNAhydroxymethylation.Demethylation.
Base excision repair.Oxidation.Glucosylation.
Deamination.
Ten-eleven translocation proteins.
Environmental health.
Epigenetics.
Environmental biosensor