Figure 1.

Active DNA demethylation in mammals. (a) The action of AID on 5-methylcytosine residues (white circles) in DNA (thick black line) gives rise to deaminated 5-methylcytosine, which can be bound by the repair glycosylase MBD4. Through yet-unknown further repair mechanisms, there is conversion into unmethylated cytosines, as shown by the disappearance of the white circles on the lower diagram. The canonical histones found in nucleosomes are colored in blue. In the accessibility model presented here, the presence (green circles) or absence of specific histone tail modifications and/or histone variants (pink spheres) guide the recruitment of the enzymes and other factors involved in the DNA demethylation. It is not yet known whether the requirement for elongator complex proteins is direct or whether they affect DNA demethylation indirectly, by a mechanism unrelated to chromatin. (b) Protection against active DNA demethylation could be linked to the presence of specific histone modifications (red circles). Non-histone proteins could be involved in this process as well.