Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes

Location, Location, Location The genome receives epigenetic marks throughout development that regulate the activity of multiple genes. One such mark is methylation, which usually represses gene transcription. Methylation has generally been studied in the promoters of genes, where many regulatory signals coordinate to control the expression of the gene. Studying neural stem cells from mice, Wu et al. (p. 444 ) now show that DNA methylation can be a double-edged sword. Although methylation of DNA sequences in promoters tends to be repressive, methylation of DNA sequences beyond the promoters can actually promote gene expression. Analysis of the methyltransferase Dnmt3a in mouse neural stem cells revealed that methylations around neurogenic genes—but outside their promoters—maintained the activity of these genes.