Methylation and a Polymorphic Restriction Site Adjacent to Human β-Interferon Gene

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Abstract
High-molecular-weight DNA from cultured human fibroblast cells and tissues was analyzed with the restriction endonucleases Msp I and Hpa II for the presence of methylated sites in the sequences flanking the β-interferon gene. The majority of the DNAs analyzed were methylated in the restriction site (CCGG) for these two enzymes and thus were sensitive to cleavage by Msp I, but resistant to Hpa II. A polymorphic Msp I restriction site was identified approximately 1000 bp upstream from the β-interferon gene. The results show an association of the β-interferon gene with Msp I fragments of either 2.7 kb or 4.2 kb, which are inherited as Mendelian alleles. An unusual Msp I site upstream from the β-interferon gene was present in 22% of the DNA from peripheral leukocytes of healthy individuals, and in 36% of the DNA from leukocytes of individuals with different forms of leukemia. Induction of β-interferon with poly(rI · rC) did not alter the methylation pattern in the sequences flanking the β-interferon gene, and the levels of β-interferon induced in cells by poly(rI · rC) could not be directly related to the presence or absence of a polymorphic Msp I restriction site in the 5′-flanking region.