Researchers complete first genome mapping of DNA modification

U.S. researchers have completed the first genome-wide mapping of a DNA modification code 5-hydroxymethylcytosine (5hmC) in embryonic stem cells.

The molecule is predominantly found in genes that are turned on, or active, according to the researchers from the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at University of California, Los Angeles.

The finding may prove to be important in controlling diseases like cancer, where the regulation of certain genes plays a role in disease development. Human embryonic stem cells were used because it had been shown previously that the molecule is abundant in those cells, as well as in brain cells.

In the study, the researchers found that 5hmC was associated with genes and tended to be found on genes that were active. The study also revealed that 5hmC was present on a type of DNA regulatory element, called enhancers, which help control gene expression. In particular, 5hmC was present on enhancers that are crucial for defining the nature of the human embryonic stem cells.The results suggest that 5hmC plays a role in the activation of genes. This is opposite of the role of the more well studied 5mC ( DNA methylation), which is involved in silencing genes. his relationship is in line with the view that 5hmC is created directly from 5mC.

If we can understand the function of 5hmC, that will lead to greater understanding of how genes are turned on and off and that could lead to the development of methods for controlling gene regulation, therefore helping control cancer and other human diseases.

5hmC is formed from the DNA base cytosine by adding a methyl group and then a hydroxy group. The molecule is important in epigenetics - the study of changes in gene expression caused by mechanisms other than changes in the DNA sequence - because the newly formed hydroxymethyl group on the cytosine can potentially switch a gene on and off. The molecule 5hmC was only recently discovered, and its function has not been clearly understood, Until now, researchers didn't know where 5hmC was located within the genome.

The study appears in the July issue of the journal Genome Biology.