Researchers at Emory University School of Medicine and the University of Chicago have developed a method for labeling and mapping a "sixth nucleotide," whose biological role scientists are only beginning to explore.
The method is described online this week in Nature Biotechnology.
The method allowed the researchers to see for the first time how 5-hydroxymethylcytosine (5-hmC) is distributed throughout the genome. Unlike 5-methylcytosine (5-mC), a chemical modification of DNA that is generally found on genes that are turned off, this extra layer of modification is enriched in active genes. 5-hmC appears to be more abundant in embryonic stem cells and brain cells, compared with other cell types, and its abundance increases substantially as the brain matures.
"The main reason why this DNA modification was not explored previously was because standard approaches didn't detect it. The groups that identified it had to isolate large amounts of DNA and analyze it directly," says co-senior author Peng Jin, PhD, professor of human genetics at Emory University School of Medicine. "I think the beauty of this work lies in how we combined an innovation in DNA chemistry with large-scale genetic analysis to achieve new insight."
In recent years, scientists have been examining the role of methylation, a modification of cytosine, one of the four bases that make up DNA (adenine, thymine, guanine are the others). When stem cells change into the cells that make up skin, blood, muscle or brain, DNA methylation helps shut inappropriate genes off. Changes in DNA methylation also underpin a healthy cell's transformation into a cancer cell.
In 2009, a second layer of modification on top of 5-mC emerged, with the discovery that 5-hmC was present in mouse brain and especially abundant in Purkinje cells, which are part of the cerebellum. While previous researchers had reported the presence of 5-hmC in human and animal DNA samples, current
|Contact: Holly Korschun|