DNA methylation in the human gamma delta beta-globin locus in erythroid and nonerythroid tissues.

We have analyzed DNA modification in the human gamma delta beta-globin gene region at 17 cleavage sites of restriction endonucleases which are unable to cleave DNA if 15-methylcytosine is present at certain positions in their respective cleavage sites. Using this criterion, all sites tested in the globin gene region are fully modified in the germ line (sperm) DNA. In somatic tissues, however, methyl groups are absent at specific sites in the globin gene region. In tissues not expressing the genes, these losses range from one of these cleavage sites in lymphocyte DNA to essentially all of these sites in the entire region in placental DNA. In the DNA of tissues expressing the globin genes, the region surrounding and including the genes expressed shows a low level of modification, whereas the neighboring DNA regions have a high level of modification. The data suggest that a low level of DNA methylation may be a necessary, but not a sufficient, condition for gene expression in higher eucaryotes.