Fig. 7. A model for DNA methylation-related glial gene chromatin remodeling during the switch from neurogenesis to gliogenesis. We have previously demonstrated that a positive-feedback loop for the JAK-STAT pathway allows for rapid activation of this pathway once it is derepressed (He et al., 2005). The time it takes to reach the threshold STAT activity for astroglial differentiation marks the onset of astrogliogenesis. DNA methylation serves as one of the key mechanisms blocking activation of the JAK-STAT pathway and glial cell lineage differentiation during the neurogenic period. Through a process of developmentally regulated DNA demethylation and active chromatin-remodeling, the JAK-STAT pathway is induced and astrocytic marker genes become responsive to STAT signaling, which marks the initiation of astrogliogenesis. In Dnmt1^–/– NPCs, hypomethylation leads to accelerated activation of the JAK-STAT pathway, shortening the time required to reach the STAT activity threshold for astrocyte differentiation, leading to precocious astrogliogenesis.