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.

Changes in DNA Methylation in Mouse Lungs after a Single Intra-Tracheal Administration of Nanomaterials

“…Several classes of environmental chemicals, including metals, particulate matter, and endocrine/reproductive disrupters, modify gene promoter methylation marks [9]. Xenobiotic exposure affects global DNA methylation (total number of methylated cytosines in the genome) and global DNA hydroxymethylation (5-hydroxymethylcytosine: 5hmC) (total number of hydroxymethylated cytosines in the genome) [10, 11]. 5hmC recently gained interest because it represents the DNA demethylation pathway [11].…”

Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation

“…5 Methylation of gene promoters and regulatory regions hinder the binding of transcription factors, leading to altered gene expression. 6 The one-carbon (I-C) metabolism plays a central role in DNA methylation, since it determines the flux of methyl-groups toward methylation of DNA. Folate, betaine, choline, and methionine are the main sources of dietary methyl-group donors in the I-C metabolism.…”

A Short-Term Fasting in Neonates Induces Breathing Instability and Epigenetic Modification in the Carotid Body

“…Epigenetic changes are implicated in many aspects of cell biology including inheritance of genes from parents, aging, and most recently, chronic diseases. Moreover, there is emerging evidence explaining “Barker’s hypothesis of fetal reprogramming” by demonstrating how epigenetic changes of genes resulting from early environmental exposures contribute to the fetal origin of the childhood/lifetime disease (Reviews in Tang and Ho 2007 ; Dao et al 2014). Our data showed that increase in global 5mC and 5-hmC content in CB DNA but not SCG DNA from mice with fasting (Fig.…”

“…Existence of 5-mC prevents binding of transcription activators at their recognized region, leading to decreased gene transcription. On the other hand, oxidation of 5-mC to 5-hydroxymethylcytosine (5-hmC) is suggested to play an important role in induction of gene transcription (Dao et al 2014). Both 5-mC and 5-hmC levels in CB and SCG DNA were measured using capture and detection antibodies followed by colorimetric quantification (ELISA kit from Zymo Research, CA).…”