DNA demethylation

Cytosine 5′ methylation of CpG dinucleotides within and around genes exerts a major influence on transcription in many plants and animals (1–3). DNA methylation can be causal for transcriptional silencing (4–5) and targets the machinery necessary to assemble specialized chromatin enriched in deacetylated histones (6–8). Once established in somatic cells, CpG methylation patterns within the genome are very stable and provide an attractive mechanism for segregating a large fraction of stably repressed chromatin (9–11). In contrast, DNA methylation is remarkably dynamic during early mammalian development and in certain tumor cells (12, 13). Alterations in the methylation status of the entire genome (14, 15), individual chromosomes (16), and specific genes (17–20) are essential for normal development (21, 22) and can promote tumorigenesis (23, 24). Understanding how these important transitions might be regulated requires the biochemical definition of the enzymatic processes that both methylate and demethylate the genome.