OL (red) differentiation and myelin (green) formation is lost when deacetylation is blocked (right).
Delaying deacetylation with a drug called VPA similarly delayed OL maturation in mice. VPA is used to treat epilepsy, but the findings suggest that it might be harmful to young children.
In neuronal and astrocyte precursors, the promoters of their fate-inducing transcription factors are inaccessible and must therefore be opened before differentiation. In OL progenitors, in contrast, it is thought that the promoters of genes such as myelin are inactive due to the presence of transcriptional inhibitors. The overall effect of deacetylation is therefore to allow myelin transcription by turning off the expression of these inhibitors.
Deacetylation was followed by histone methylation, which more permanently silences gene expression. By starting with (reversible) deacetylation, OL progenitors probably maintain some plasticity in early stages of differentiation.