Figure 6.

NCOR and HDACs Play Nonredundant Roles in the Regulation of Neural Stem Cell Differentiation

In multipotent embryonic NSCs, SMRT and HDAC3 are nonredundantly repressing neuronal differentiation, at least in part by repressing Bdnf expression required for the cell survival during the progression of neuronal differentiation. Astrocytic differentiation is repressed by both NCOR and SMRT. Oligodendrocyte differentiation is repressed by NCOR and HDAC2 in neural stem cells by repressing different OL-associated genes. In Oli-neu cells (prenatal oligodendrocyte progenitors), a repression of Sox10 is maintained by HDAC2 that occupies the regulatory U2 enhancer of Sox10. In CG4 cells (postnatal oligodendrocyte precursors), Sox10 is not only required for the progression of OL differentiation but also for retaining a more differentiated state by being required for efficient repression of Sox2 along with Sox9, Hes5, and other progenitor associated genes.