OLIG2 is a master regulator for oligodendrocyte lineage specification, especially regulating key stages of early oligodendrocyte development9–13. OLIG2 has been reported to be a upstream regulator of SOX10, another master regulator in oligodendrocyte development13. In addition, it has been demonstrated that OLIG2 recruits SWI/SNF chromatin remodeling enzyme SMARCA4 (also known as BRG1) to potentiate the expression of several myelin-related factors to initiate OPCs differentiation into iOLs7. Interestingly, OLIG2 has been reported to determine the cell fate of motor neurons, but acts as a gene repressor14–16. During the switching process of cell fate, master regulators genome-widely reconstruct epigenetic patterns, which subsequently guides the new transcriptomes17. H3K9me3 modification is one of the most predominant approaches for gene deactivation epigenetically, which is vital in embryonic development and reprogramming18. Deficiency of SETDB1, a major tri-methyltransferase of H3K9me3 leads to stem cell necroptosis in gut19.
