The summary of the findings presented in our study is illustrated in Figure 8. First, expression of Mecp2 isoforms was significantly and reciprocally changed at different stages of NSC differentiation, in association with minor but significant changes in DNA methylation at selected Mecp2 REs, suggesting possible involvement of these regions in Mecp2 regulation. Second, treatment of differentiating NSC with decitabine for 48 h led to demethylation of specific Mecp2 REs (promoter R2 and all intron 1 regions) and subsequent upregulation of Mecp2e1/MeCP2E1 (but not Mecp2e2), implying the differential sensitivity of the two Mecp2 isoforms to decitabine. Such differential sensitivity of Mecp2 isoforms to decitabine might be useful in future drug therapies to specifically activate one isoform but not the other. Furthermore, the ability of decitabine to induce Mecp2e1/MeCP2E1 at both transcript and protein levels provide insights for future therapeutic strategies for MeCP2 deficiency-related neurodevelopmental disorders such as autism and Rett syndrome. Finally, the significant and dynamic (positive or negative) correlation between the expression of Mecp2 isoforms and DNA methylation implies the potential contribution of these REs in regulating Mecp2 isoforms
