DNA Hydroxymethylation: Implications for Toxicology and Epigenetic Epidemiology

Pulczinski, Jairus C.; Yeung, Bonnie H.Y.; Wu, Qian; Cheng, Robert; Tang, Wan Yee

doi:10.1016/b978-0-12-812433-8.00008-3

Cited by 1 publication

(1 citation statement)

References 156 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While DNA methylation has been extensively investigated, knowledge about how 5hmC patterns change in response to adverse environmental factors is so far scarce [43]. Up-to-date information is focused on brain-related 5hmC changes upon external exposures [44] or has been reviewed in terms of the link between environmental cues and DNA hydroxymethylation, lacking discussion of the underlying molecular mechanisms [45]. The present paper consolidates current evidence on 5hmC pattern alterations induced by environmental factors in different organs, tissues, and cell lines and analyzes how they affect genome function.…”

Section: Introductionmentioning

confidence: 99%

Environmental Epigenetics and Genome Flexibility: Focus on 5-Hydroxymethylcytosine

Efimova

Koltsova

Krapivin

et al. 2020

IJMS

View full text Add to dashboard Cite

Convincing evidence accumulated over the last decades demonstrates the crucial role of epigenetic modifications for mammalian genome regulation and its flexibility. DNA methylation and demethylation is a key mechanism of genome programming and reprogramming. During ontogenesis, the DNA methylome undergoes both programmed changes and those induced by environmental and endogenous factors. The former enable accurate activation of developmental programs; the latter drive epigenetic responses to factors that directly or indirectly affect epigenetic biochemistry leading to alterations in genome regulation and mediating organism response to environmental transformations. Adverse environmental exposure can induce aberrant DNA methylation changes conducive to genetic dysfunction and, eventually, various pathologies. In recent years, evidence was derived that apart from 5-methylcytosine, the DNA methylation/demethylation cycle includes three other oxidative derivatives of cytosine—5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine. 5hmC is a predominantly stable form and serves as both an intermediate product of active DNA demethylation and an essential hallmark of epigenetic gene regulation. This makes 5hmC a potential contributor to epigenetically mediated responses to environmental factors. In this state-of-the-art review, we consolidate the latest findings on environmentally induced adverse effects on 5hmC patterns in mammalian genomes. Types of environmental exposure under consideration include hypnotic drugs and medicines (i.e., phenobarbital, diethylstilbestrol, cocaine, methamphetamine, ethanol, dimethyl sulfoxide), as well as anthropogenic pollutants (i.e., heavy metals, particulate air pollution, bisphenol A, hydroquinone, and pentachlorophenol metabolites). We put a special focus on the discussion of molecular mechanisms underlying environmentally induced alterations in DNA hydroxymethylation patterns and their impact on genetic dysfunction. We conclude that DNA hydroxymethylation is a sensitive biosensor for many harmful environmental factors each of which specifically targets 5hmC in different organs, cell types, and DNA sequences and induces its changes through a specific metabolic pathway. The associated transcriptional changes suggest that environmentally induced 5hmC alterations play a role in epigenetically mediated genome flexibility. We believe that knowledge accumulated in this review together with further studies will provide a solid basis for new approaches to epigenetic therapy and chemoprevention of environmentally induced epigenetic toxicity involving 5hmC patterns.

show abstract

Section: Introductionmentioning

confidence: 99%