Pass the SunnyD. According to a paper just out in the Journal of Biological Chemistry, vitamin C, also known as ascorbic acid, may have a role in epigenetic regulation, specifically 5-hmC regulation. Gaofeng Wang at the University of Miami Miller School of Medicine and colleagues demonstrated that this critical dietary nutrient is involved in hydroxylation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in DNA, a reaction catalyzed by Tet methylcytosine dioxygenase.
This enzyme belongs to the Tet family proteins which, in turn, belong to the iron and 2-oxoglutarate-dependent dioxygenase superfamily. These enzymes catalyze the hydroxylation of many substrates, including methylated nucleic acids and proteins.
The investigators found:
- The amount of 5-hmC was extremely low in mouse embryonic fibroblasts that were cultured in ascorbate-free medium. But when ascorbate was added in a dose- and time-dependent fashion, the amount of 5-hmC rose without affecting the expression of Tet genes.
- Treatment with the glutathione, a reducing agent, did not affect levels of 5-hmC
- Preventing the entry of ascorbate into cells and knocking down the expression of several Tet genes using short interference RNA technology inhibited the effect of ascorbate on 5-hmC.
Based on their data, the team concluded that ascorbate probably acts as a cofactor for Tet methylcytosine dioxygenase to hydroxylate 5-mC. Wang and colleagues say in the paper, “Our data support ascorbate as a critical mediator of the interface between the genome and environment.”
So grab some OJ and click over to Journal of Biological Chemistry, April 2, 2013