Gene profiles regulated and targeted by PRC2 in oligodendrocyte lineage cells

The PRC2 complex creates a repressive mark histone-H3-Lys27-trimethylation. Although PRC2 is involved in various biological processes, its role in glial development remains ambiguous. We find PRC2 complex is required for oligodendrocyte (OL) differentiation and myelination, but not for OL precursor formation. Furthermore, most PRC2-null OL lineage cells (cKO) acquire astrocyte features. RNA profiles from RNAseq assay reveal that many transcription factors involved in oligodendrocyte and astrocyte development are regulated by PRC2. Moreover, PRC2-null OL lineage cells aberrantly induce Notch-NFIA and Wnt pathway genes. The chromatin immunoprecipitation-sequencing (ChIPseq) assay further reveals that PRC2 is recruited to many of Notch-NFIA and Wnt pathway genes. The datasets demonstrate the molecular program underlying the specific action of PRC2 and suggest PRC2 as a gatekeeper that determines the timing of OL lineage progression and myelination. Overall design: Examination of RNAseq profiles in the culture of OL lineage cells in proliferative and differentiating conditions from control and PRC2-cKO brain, and ChIPseq profiles in P3 spinal cords when and where OL precursors and differentiating OLs reside.