Newfound roles of OLIG2 in the regulation of lncRNAs, epigenetic status and its own expression at transcriptional and post-transcriptional levels during oligodendrocyte lineage formation

We performed an integrated study of genome-wide OLIG2 binding and the epigenetic modification status of both coding and non-coding genes during three stages of oligodendrocyte differentiation in vivo: Neural Stem Cells (NSC), Oligodendrocyte Progenitor Cells (OPC), and Newly Formed Oligodendrocytes (NFO). We found that 613 lncRNAs have OLIG2-binding sites and are expressed in at least one cell type, which can potentially be activated or repressed by OLIG2. 48 of them have increased expression in oligodendrocyte lineage cells. Predicting lncRNA functions by using a “guilt-by-association” approach revealed that the functions of these 48 lncRNAs were enriched in 'oligodendrocyte development and differentiation'. Additionally, bivalent genes are known to play essential roles during embryonic stem cell differentiation. We identified bivalent genes in NSC, OPC, and NFO, and found that some bivalent genes bound by OLIG2 are dynamically regulated during oligodendrocyte development. Importantly, we have identified AU-rich elements (AREs) in the 3'-UTRs of Olig2 mRNAs. We unveiled a previously unknown mechanism that, in addition to transcriptional regulation via DNA binding, OLIG2 could post-transcriptionally self-regulate expression through interaction with the 3'-UTR of its own mRNA. Overall design: Oligodendrocyte development from NSC