Stem Cells Have Unusual Base

5-Formylcytosine, a novel genetic base, has been discovered in embryonic stem cell DNA. The new base is modified in the same position of cytosine where methyl groups involved in gene silencing are sometimes found (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201103899). Until 2008, only DNA’s four genetic bases—adenine, thymine, guanine, and cytosine—and methylated cytosines—a gene’s “off switch”—were thought to populate the healthy genome of cells. Then 5-hydroxymethylcytosine was found decorating the DNA of a wide variety of cell types. Scientists began racing to determine the exact biological role of this so-called epigenetic mark—a race still in progress. Researchers led by Thomas Carell of Ludwig Maximilian University, in Munich, uncovered 5-formylcytosine, but they haven’t determined its biological role either. Both unusual bases are likely involved in the transformation of a fertilized egg into a pluripotent embryonic stem cell, the researchers believe. “This work is the first step toward addressing this intriguing and important issue,” comments University of Chicago biochemist Chuan He. “Next, the study of the biological roles and fates of 5-formylcytosine will be key to assess its importance.”