DNA Methylation and the Expression of Human Interferon Alpha-1-Related Genes and the Beta-I Gene

Abstract

The methylation pattern of the α1-related and the β1, interferon (IFN) genes was investigated by digestion of cellular DNA obtained from human lymphoblastoid (Namalwa) and diploid human fibroblast (FS4) cell lines with the isoschizomeric restriction endonucleases Mspl and Hpa II followed by Southern blot-hybridization using IFN-α1 and IFN-β1 cDNA probes. The IFN genes in these cells can be induced to produce different relative amounts of the α and β type IFNs depending upon the combination of cell type and inducer used. Even though the IFN-α1 related genes are known to be highly expressible in Namalwa cells (following induction with Sendai virus) they are present in a hypermethylated state. In FS4 cells, however, despite the fact that these genes do not appear to be particularly inducible, their level of methylation is lower than that seen in Namalwa cells. The IFN-β1 gene, on the other hand, is hypermethylated in Namalwa cells and expressed poorly in this cell type. It is relatively less methylated in FS4 cells where it can be expressed at high levels. These experiments indicate that the level of methylation of IFN genes correlates with the cell type investigated but not with which particular IFN gene is expressed. Furthermore, our experiments also demonstrate that the levels of methylation of the IFN genes are not altered during interferon induction.