Mosaic methylation of the repeat unit of the human ribosomal RNA genes.

The pattern of methylation in human genes for 18S and 28S ribosomal RNA has been investigated using methylation-sensitive restriction enzymes. We find that the transcribed region of the repeat unit is predominantly unmethylated, in agreement with previous studies. In contrast the non-transcribed spacer, which makes up the majority of the 43 kb repeat unit, is highly methylated in blood cell DNA. The boundaries between methylated and non-methylated domains appear to be relatively sharp, and occur approximately 1.5 kb upstream of the 5' edge of the proximal promoter and approximately 1.0 kb downstream of the 3' end of the transcribed region. A small proportion of all repeat units are methylated throughout the transcribed region, and may represent silent genes. The coincidence between the methylation pattern, the transcription pattern and other features of the repeat unit has implications for our understanding of the mechanism by which patterns of DNA methylation are generated.