Then we performed H3K9me3 ChIP-seq in control and Setdb1 mutant iOLs prepared from mouse brain. H3K9me3 peak density was most diminished around those gene loci occupied by OLIG2 in the iOLs from mutant mice (Supplementary Fig. 7a). Inhibition of SETDB1 and overexpression of OLIG2-VP64 caused similar upregulated DEGs, as revealed by GO analysis (Supplementary Fig. 7b, c). Pro-myelinogenesis genes including Enpp6, Sox10, Plp1, Mbp, Cnp and Mag were downregulated as expected in two transcriptomes (Fig. 6a, b). Sox1134 and Hes135 (Supplementary Fig. 7d) are two inhibitory transcriptional factors for myelin. Their levels were increased in two transcriptomes (Fig. 6a, b), which was not observed for other well-known transcriptional factors with anti-myelinogenesis properties (Fig. 6c, d). However, only Sox11 but not Hes1 silencing restored the capacity of myelinogenesis in the Setdb1-deficient rat OPCs (Fig. 6e–g and Supplementary Fig. 7e, f). Sox11 loci were occupied with OLIG2 and modified with H3K9me3 (Fig. 6h), and H3K9me3 density was reduced in the promoter region of Sox11in the Setdb1 mutant iOLs (Supplementary Fig. 7g). ChIP-qPCR assay was performed to confirm the decreased H3K9me3 enrichment when
