|Methyl groups added to DNA. Image by Christoph Bock (Max Planck Institute for Informatics) on Wikimedia commons|
Not all genes in a cell are active all the time. Genes can be turned “off” by chemical alterations to the DNA in the form of small molecules called methyl groups. As an animal or plant develops, more and more methyl groups are added to its DNA. This process is usually not reversible during an organism’s lifetime--once a gene is turned off during development it doesn't generally turn back on.
During a key period, just after a sperm and egg merge to create a new embryo, many of these methyl groups are kicked off the DNA for a short time by a group of enzymes, called “Tet” enzymes. This turns on the genes a developing embryo needs for a short time. As the embryo develops, the cycle of adding methyl groups to DNA starts all over again.
The research team, led by Miguel Ramalho-Santos, found that Tet enzymes work much better for mouse embryonic stem cells when Vitamin C is added to the cells' nutrient broth. They reported their findings on June 30 in the scientific journal, Nature. The researchers were not looking for this property of Vitamin C -- they stumbled across it while testing different nutrient broths.
Stem cell researchers could use this finding to improve the growth rate and stability of cells in their labs. In the long term, doctors working on in vitro fertilization could use vitamin C to improve the health of young embryos before they are implanted. The discovery could also lead to a new cancer treatments, which often occur when the mechanism to turn genes on or off go haywire.
Humans, unlike most animals, can’t make their own Vitamin C and must get it from the food they eat. A lack of Vitamin C in a person’s diet can lead to scurvy, a disease caused by the malfunction of another enzyme that requires Vitamin C to form connective tissues such as collagen. The disease is rare now, but was common in sailors during the seventeenth and eighteenth centuries.
In late 2009, scientists in China found that vitamin C also helped the process of creating induced pluripotent stem (iPS) cells.
The role that Tet enzymes play in DNA regulation was discovered just a few years ago, also in 2009, by one of the study’s co-authors, Anjana Rao (another CIRM grantee), now at the La Jolla Institute for Allergy and Immunology. The researchers’ next plans are to study how vitamin C affects gene expression and Tet enzymes in living animals.
CIRM Funding: Miguel Ramalho-Santos (RS1-00434)