Considering that OLIG2 has dual roles in both gene activation and deactivation, it is feasible to break down OLIG2-mediated inhibitory complex rather than wipe OLIG2 itself off. Master regulators often cooperate with epigenetic factors to regulate gene expression. We took a proteomics approach to identify the key components that binds to Olig2 for transcriptional regulation (Supplementary Fig. 2a). The capture of known coactivator BRG1 highlights the reliability of proteomic experiments (Fig. 2a). DNA or histone methylation triggers gene deactivation. Enzymes fulfilling DNA methylation such as DNMT1 or DNMT3a were not found to be interacting with OLIG2; but factors of histone modification were enriched (Fig. 2b). H3K9 or H3K27 methylation results in gene repression. Enzymes and cofactors mediating H3K9 but not H3K27 methylation were identified, such as SETDB1, TRIM28 (also known as KAP1), EHMT1 (also known as GLP), EHMT2 (also known as G9a), etc (Fig. 2a)22,23. That H3K9 but not H3K27 methylation is mentioned for regulation of OPC differentiation by Liu et al.24. If OLIG2 inhibits gene expression through H3K9 methylation to promote myelination, then disrupting H3K9 methylation will also affect
