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.