As indicated in the Figure above, captioned "Demethylation of 5-methylcytosine," the first step in active demethylation is a TET oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). The demethylation process, in some tissues and at some genome locations, may stop at that point. As reviewed by Uribe-Lewis et al., in addition to being an intermediate in active DNA demethylation, 5hmC is often a stable DNA modification. Within the genome, 5hmC is located at transcriptionally active genes, regulatory elements and chromatin associated complexes. In particular, 5hmC is dynamically changed and positively correlated with active gene transcription during cell lineage specification, and high levels of 5hmC are found in embryonic stem cells and in the central nervous system. In humans, defective 5-hydroxymethylating activity is associated with a phenotype of lymphoproliferation, immunodeficiency and autoimmunity.