Abstract
It has become apparent that epigenetic modification plays a critical role in the regulation of lineage-specific gene expression. We have previously reported that the change in DNA methylation at the promoter of astrocytic genes, such as glial fibrillary acidic protein (GFAP), controls the switch from neurogenesis to astrocytogenesis in the developing telencephalon. The methylated promoter at midgestation undergoes demethylation as gestation proceed, corresponding to the onset of astrocytogenesis. However, the exon1 of the gene remains hypermethylated even in the adult neural progenitors and in cells differentiated from the progenitors, i.e. neurons, astrocytes and oligodendrocytes. The methyl-CpG binding proteins (MBDs) bind to methylated DNA and suppress the target gene expression. They are strongly expressed only in neurons in the nervous system and the cells do not respond to astrocyte-inducing signals to express GFAP. In contrast, by using Cre-recombinase fate tracing, we show here that oligodendrocytes, in which MBDs are not expressed, expressed GFAP upon stimulation with the astrocyte-inducing cytokines. Overexpression of MeCP2, one of the MBD family proteins, in oligodendrocytes inhibited the GFAP expression by the cytokines, implicating MBDs as key molecules to restrict the transdifferentiation of neural cells. It is well known that astrocytes increase dramtically in number after insult to the nervous systems. Taking the above results into consideration, oligodendrocytes could be a source of the newly generated astrocytes in damaged nervous systems in vivo. [J Physiol Sci. 2006;56 Suppl:S46]
