and most of OPCs are dormant33. Depleting Setdb1 in the OLs at P60 had no notable impact on the myelination throughout our experimental timeframe (up to P90) (Supplementary Fig. 6o-q). TdT-mediated dUTP Nick-End Labeling (TUNEL) assay failed to detect obvious cell death in Setdb1 mutant brains (Supplementary Fig. 6r). Together, these different mouse models demonstrate a temporary function of SETDB1 repressive complex in the early but not late stage of OPC differentiation and that SETDB1 is indispensable for the maintenance of myelin.