Maeder, M.L. et al. Nat. Biotechnol. doi:10.1038/nbt.2726 (9 October 2013).

Methylation of DNA at cytosine bases is an important mechanism to regulate gene expression, but studying the functional role of this epigenetic change requires specific methods to demethylate CpGs in a targeted manner in the genome. Maeder et al. describe an approach for demethylating cytosine that involves fusing the human TET1 hydroxylase catalytic domain to engineered transcription activator–like effector (TALE) repeats. This framework can be programmed to target essentially any DNA sequence using the TALE repeat code, and it allowed the authors to induce locus-specific demethylation at three endogenous genes in three different human cell lines and study the effects on gene expression. The authors found that the efficiency of the process depended on the genomic locus that was targeted. Control experiments accounted for off-target and nonspecific effects. The method provides researchers with a useful tool for studying the functional significance of epigenetic events.