Developmental stage dependent regulation of DNA methylation and chromatin modification in a immature astrocyte specific gene promoter.

Astrocytes are generated from neuroepithelial cells after neurons during brain development. However, the mechanism of this sequential generation is not fully understood. Here, we show that a particular cytosine residue in the promoter of the gene encoding the immature astrocyte marker, S100beta, becomes demethylated, correlating with the time when the S100beta expression commences at embryonic day (E) 14. In addition, astrocyte-inducing cytokine, BMP2, increased histone acetylation around the CpG site in neuroepithelial cells at E14 but not E11 when S100beta expressing astrocytes are absent. Furthermore, binding of a methyl DNA binding protein, MeCP2, to the S100beta gene promoter in neuroepithelial cells was reduced at E14 compared to E11. Thus, demethylation of specific CpG site is suggested to be a critical determinant in regulating astrocyte differentiation in the developing brain.