Genome-wide hydroxymethylcytosine pattern changes in response to oxidative stress

Area of Science:

• Epigenetics and DNA modification
• Oxidative stress biology
• Gene regulation

Background:

• TET enzymes catalyze the conversion of methylcytosine to hydroxymethylcytosine.
• The role of TET enzymes in response to oxidative stress is not well-established and lacks in vivo evidence.

Purpose of the Study:

• To investigate the impact of in vivo oxidative stress on the global hydroxymethylome.
• To identify specific genomic regions affected by oxidative stress-induced changes in hydroxymethylation.

Main Methods:

• Treatment of cells with buthionine sulfoximine to induce oxidative stress.
• Depletion of major antioxidant enzymes (GPx1 and 2) in mice.
• Genome-wide profiling to map hydroxymethylated regions.

Main Results:

• A global decrease in hydroxymethylcytosine was observed in cells and mice under oxidative stress.
• Differentially hydroxymethylated regions were identified in coding genes and microRNA genes.
• Affected genes are involved in the cellular response to oxidative stress.

Conclusions:

• In vivo oxidative stress profoundly affects the global hydroxymethylome.
• Hydroxymethylation patterns in both coding and microRNA genes are sensitive to oxidative conditions.
• These findings highlight a significant link between oxidative stress and epigenetic regulation via hydroxymethylation.