The elusive role of 5′-hydroxymethylcytosine

Abstract

5′-hydroxymethylcytosine (5hmC) is a variant of the common covalent epigenetic modification of DNA 5′-methylcytosine (5mC). Although the presence of this modified base in mammalian DNA has been recognized for several decades, it has recently gained center stage as a suspected intermediate in enzymatic active demethylation of 5mC. The role of 5hmC remains elusive in spite of a large body of studies. It is proposed that 5hmC is a variant of the 5mC epigenetic signal and is involved in epigenetic regulation of gene function. Recent data support a role for 5hmC in the activation of lineage-specific enhancers.