Whether its pop culture (like the ongoing royal baby mania) or cell culture, there’s no denying the enormous impact that ‘media’ has on our life. In fact, new evidence shows that a little Vitamin C in cell culture media can influence mouse embryonic stem (ES) cells, like typical pre-teens, to undergo a blastocyst-like identity crisis.
Intriguingly, most cell culture media lacks vitamin C. This fact has opened a new frontier of research for examining how the epigenome serves as the bridge between nature and nurture. It has recently been shown that vitamin C acts as a cofactor for Tet methylcytosine dioxygenase (Tet) to hydroxylate 5mC. At the same time, other groups have shown 5hmC has an important role in establishing transient marks in (brain) development. But now a team of ‘Buccaneers’ from UCSF and UBC have brought these findings together and shown that 5-hmC just can’t get enough of the spotlight. Here’s what they found:
- Vitamin C induces loss of cytosine methylation (5mC) at gene promoters through a rapid and global (but temporary) increase in 5hmC.
- Vitamin-C-induced DNA demethylation leads to increased expression of many germline genes.
- “The effects of vitamin C are Tet-dependent”, with enrichment for Tet binding near the transcription start site of genes being affected by vitamin C treatment.
- Intriguingly, vitamin C, but not other antioxidants (like glutathione or dithiothreitol (DTT)), enhances Tet activity. This dependency was further confirmed by the observation “the vitamin-C-induced changes in 5hmC and 5mC are entirely suppressed in Tet1 and Tet2 double knockout ES cells.”
- Ultimately, “the results of this study establish vitamin C as a direct regulator of Tet activity and DNA methylation fidelity in ES cells.”
In addition to having a new excuse to instill Flintstone vitamin addiction upon future generations, the implications of this research are far reaching, so we got in contact with Senior author Dr. Lorincz. He shared his surprise to the finding “that the simple addition of vitamin C to ES cell culture medium leads to a rapid and widespread decrease in the level of DNA methylation in ESCs, yet the regions resistant to DNA demethylation i.e. those that remain methylated- are similarly resistant to DNA demethylation in the preimplantation embryo, indicating that cells cultured under these conditions may more closely approximate the ICM stage of development than ESCs cultured in the absence of Vitamin C”.
These findings also open up new avenues of research and Dr. Lorincz posed a few potential questions that his group’s work has opened up:
- “How would the addition of vitamin C to the culture media used for in vitro fertilization influence the epigenome in general and imprinted regions in particular?”
- “Given that humans cannot synthesize vitamin C, how does maternal dietary vitamin C intake level influence the methylome of the offspring?”
- “In cancers associated with hypomorphic mutations in the tet2 gene and aberrant hypermethlyation, such as in myeloid cancers or T-cell lymphoma, would vitamin C treatment have a therapeutic effect?”
Dr. Lorincz concludes that these “results reveal that vitamin C can profoundly influence the methylome of cells in vitro.”
Get your daily dose at Nature, July 2013