The observed negative correlation between the expression of both Mecp2 isoforms and Mecp2 promoter elements are novel and are in accordance with previous correlation studies on the human MECP2 expression and promoter DNA methylation [2,19]. Furthermore, our study is novel in demonstrating a dynamic (positive/negative) correlation between the intronic DNA methylation and expression of Mecp2 isoforms in differentiating brain cells. It is possible that the promoter regions analyzed in our study (which also overlap with the core Mecp2 promoter [13]) might be shared by both Mecp2 isoforms, whereas depending on the stage of neural differentiation, intron 1 regions may add another layer of regulation for Mecp2 isoform-specific expression. Supporting our findings, the role of intronic DNA methylation in regulating gene expression of other genes has been previously reported [70,71]. Several other reports also show evidence that gene expression negatively correlates with promoter methylation and positively correlates with gene-body methylation [67,72].
