OL (red) differentiation and myelin (green) formation is lost when deacetylation is blocked (right).
Many progenitor cell types start differentiation by turning on transcription. But on
page 577, Shen et al. show that oligodendrocytes (OLs)—the myelin-forming cells of the nervous system—require a general transcriptional shutdown for differentiation.The transcriptional slowing is due to histone deacetylation, which compacts chromatin. The authors find that histone H3 must be deacetylated for OL progenitors to start differentiating after they exit the cell cycle. Although this shuts off many genes, typical OL proteins such as myelin were only expressed after global deacetylation, which normally occurred in mice during the first two weeks after birth. This timing might coincide with reduced levels of mitogens, which inhibit deacetylation.
Delaying deacetylation with a drug called VPA similarly delayed OL maturation in mice. VPA is used to treat epilepsy, but the findings suggest that...
