In an article recently published in Genome Biology, Michael Rehli and colleagues of the University Hospital Regensburg have identified novel examples of active DNA demethylation that are coupled to the appearance of ‘activating’ histone modifications.
Until now, the majority of evidence for active, replication-independent DNA demethylation in mammalian systems has relied upon inhibiting cell division using pharmacological inhibitors and monitoring any subsequent DNA methylation. Here, the authors avoid the use of inhibitors by investigating DNA demethylation in a differentiation system; that of human peripheral blood monocytes into macrophages or dendritic cells in which differentiation proceeds without cell division. By monitoring genome-wide methylation levels during a time course of differentiation, the authors were able to identify novel sites of active demethylation. By analysing histone modifications at these sites, they also found that active DNA demethylation correlated with the increase in ‘activating’ histone modifications.
While the enzymes involved in this active DNA demethylation process remain unknown, the characterisation of active demethylation sites and their associated histone modifications is an important step toward identifying these enzymes.