Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells

The modified DNA base 5-hydroxymethylcytosine (5hmC), sometimes called the sixth base, is present in the mammalian genome where it is generated by oxidation of 5-methylcytosine (5mC; the fifth base) by enzymes of the Tet family. Four papers in this issue, from the Helin, Zhang, Rao and Reik laboratories, respectively, report on the genome-wide distribution of Tet1 and/or 5hmC in mouse embryonic stem cells using the ChIP-seq technique. Links between Tet1 and transcription regulation both activation and repression are revealed. Anjana Rao and colleagues also describe two alternative methods with increased sensitivity for mapping single 5hmC bases. In the associated News & Views, Nathalie Vron and Antoine H. F. M. Peters discuss what these and other recent papers reveal about the role of Tet proteins in regulating DNA methylation and gene expression.