Transgene methylation in mice reflects copy number but not expression level

In mammals, CpG methylation is one of the mechanisms of epigenetic control over the linear sequence of bases of deoxyribonucleic acid (DNA); about 70% of CpG dinucleotides are methylated. The actual signal that triggers DNA methylation is not known, although repetitive DNA has been shown to be an attractive template for DNA methylases. To address methylation events associated with transgenic copy number, we have analyzed transgenes that are actively transcribed in a tissue-specific manner. We have compared gross transgene methylation by restriction-enzyme digestion in expressing and nonexpressing tissues. The observed pattern suggests that the DNA methylation machinery can recognize repeated genomic sequences independently of their transcriptional activity.