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.
Namihira
Masakazu
M
Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
Nakashima
Kinichi
K
Taga
Tetsuya
T
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D015226:Dinucleoside Phosphates / Q000378:metabolism; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009414:Nerve Growth Factors / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism
D002843:Chromatin; D017931:DNA Primers; D015226:Dinucleoside Phosphates; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C015772:CpG dinucleotide