Transposable elements: targets for early nutritional effects on epigenetic gene regulation

Area of Science:

• Epigenetics
• Developmental Biology
• Nutritional Science

Background:

• Early nutrition is known to influence adult metabolism in mammals.
• Epigenetic mechanisms, such as DNA methylation, are implicated in mediating these effects.
• Transposable elements can influence gene regulation and are potentially sensitive to epigenetic changes.

Purpose of the Study:

• To investigate if early methyl donor nutrition can alter the epigenetic status of transposable elements.
• To test the hypothesis that metastable methylation sites in transposable elements are epigenetically labile.
• To examine the impact of maternal methyl supplementation on offspring phenotype and the A(vy) locus methylation.

Main Methods:

• Utilized viable yellow agouti (A(vy)) mice, which contain a transposable element in the agouti gene.
• Supplemented the diet of a/a dams with methyl donors (folic acid, vitamin B12, choline, betaine).
• Assessed offspring phenotype and analyzed CpG methylation status at the A(vy) locus.

Main Results:

• Dietary methyl supplementation of dams resulted in altered phenotypes of A(vy)/a offspring.
• Increased CpG methylation at the A(vy) locus was observed in offspring from supplemented dams.
• The A(vy) transposable element was identified as conferring epigenetic metastability and lability.

Conclusions:

• Early nutritional interventions, specifically methyl donor supplementation, can epigenetically modify gene regulation.
• The A(vy) transposable element's methylation status is sensitive to maternal diet during early development.
• Findings suggest potential unintended deleterious effects of dietary supplementation on human epigenetic gene regulation.