Olig2 Recruits Setdb1 For Gene Repression In Myelinogenesis

When tissues start specification from embryonic stage,bunch of genes’expressions were orchestrated.Some genes are activated,while some are repressed.In these well-organized processes,there always are one or two most important transcriptional factors,which is named master regulator,controlling the whole tissue specific transcriptional machine.More and more master regulators,in other tissues,were reported to govern the differentiation process in multiple transcriptional regulation.They play activator roles on some gene loci,and in the meantime,they repress genes on other loci.The effect on transcription regulation is depending on the context which cofactor they recruit,mostly some epigenetic modifiers.Master regulator Olig2 should have both transcriptional activation and repression functions in oligodendrocyte genesis.The expression of Olig2 is highly specific in oligodendrocyte lineage and motor neuron lineage.Even though Olig2 has been reported to be an essential activator in OPC differentiation by recruit Brgl,an ATP-dependent chromatin remodeler,we found the hint that Olig2 may have a repressor function in OPC differentiation by analyzing several sequencing data reported.Furthermore,we revealed that Setdb1,recruited by Olig2,functioned as major executor to repress a set of genes,such as Soxll,which need downregulated upon OPC differentiation.Our experiments show that repressor role of master regulator Olig2 is necessaryto myelination in central never system.And Setdb1 is also an inportant player for oligodendrocyte development and meylin regeneration in mice.And these results also lay the foundation for clinical research.