5-Hydroxymethylcytosine (5hmC), or How to Identify Your Favorite Cell

Recently described as the sixth base of the DNA macromolecule, the precise role of 5-hydroxymethylcytosine (5hmC) is the subject of debate. Early studies indicate that it is functionally distinct from cytosine DNA methylation (5mC), and there is evidence for 5hmC being a stable derivate of 5mC, rather than just an intermediate of demethylation. Moreover, 5hmC events correlate in time and space with key differentiation steps in mammalian cells. Such events span the three embryonic germ layers and multiple progenitor cell subtypes, suggesting a general mechanism. Because of the growing understanding of the role of progenitor cells in disease origin, we attempted to provide a detailed summary on the currently available literature supporting 5hmC as a key player in adult progenitor cell differentiation. This summary consolidates the emerging role for 5hmC in defining cellular fate.