The epigenetic landscape of oligodendrocyte progenitors changes with time
Adult oligodendrocyte progenitors (aOPCs) generate myelinating oligodendrocytes, like neonatal progenitors (nOPCs), but they also display unique functional features. Here, using RNA-sequencing, unbiased histone proteomics analysis and ChIP-sequencing, we define the transcripts and histone marks underlying the unique properties of aOPCs. We describe the lower proliferative capacity and higher levels of expression of oligodendrocyte specific genes in aOPCs compared to nOPCs, as well as the greater levels of H4 histone marks. We also report increased occupancy of the H4K8ac mark at chromatin locations corresponding to oligodendrocyte-specific transcription factors and lipid metabolism genes. Pharmacological inhibition of H4K8ac deposition reduces the levels of these transcripts in aOPCs, rendering their transcriptome more similar to that of nOPCs. The repressive H4K20me3 mark is also higher in aOPCs compared to nOPCs and pharmacological inhibition of its deposition results in increased levels of genes related to the mature oligodendrocyte state. Overall, this study identifies two histone marks which are important for the unique transcriptional and functional identity of aOPCs.