Abstract
The interplay of transcription factors and epigenetic modifiers, including histone modifications, DNA methylation and microRNAs during development is essential for the acquisition of specific cell fates. Here, we review the epigenetic "programming" of stem cells into oligodendrocytes, by analyzing three sequential stages of lineage progression. The first transition from pluripotent stem cells to neural precursors is characterized by repression of pluripotency genes and restriction of the lineage potential to the neural fate. The second transition from multipotential precursors to oligodendrocyte progenitors is associated with the progressive loss of plasticity and the repression of neuronal and astrocytic genes. The last step of differentiation of oligodendrocyte progenitors into myelin-forming cells is defined by a model of derepression of myelin genes.