BRG1 programs PRC2-complex repression and controls oligodendrocyte differentiation and remyelination

Mutations in Brg1 can cause Coffin-Siris syndrome, where a patient had white matter defects and partial agenesis of the corpus callosum; however, Brg1 functions in CNS myelination and remyelination is unsure. We show that PDGFRa expressed prior than NG2, depletion of Brg1 at PDGFRa+ OPC leads to OPC differentiation restriction and myelin defects, also, Brg1 is critical for oligodendrocyte remyelination. Genomic occupancy and transcriptome analyses indicate that Brg1 promotes H3K27me3 and neuronal genes. Thus our findings reveal that Brg1 is a critical epigenetic programmer of CNS myelination and repair through recruiting H3K27me3 and neuronal genes, suggesting potential strategies of therapeutic intervention for Brg1-associated white matter defects. Overall design: 2 Control Samples and 2 Mutant