Increased expression of IAP elements in tumor cells compared with normal cells is accompanied by extensive hypomethylation of IAP sequences. We have used oligonucleotide probes based on sequences in the LTRs of expressed IAP elements to examine the methylation state of subsets of the endogenous IAP proviral sequences, and have found that multiple common IAP loci were hypomethylated in B-cell tumors. However, not all IAP elements were hypomethylated even when their LTR sequences were very similar, suggesting that the methylation state of the proviral DNA is determined by their position in the genome. More IAP loci were hypomethylated in tumors derived from mature B-cells than in tumors derived from pre-B cells, suggesting that the hypomethylation patterns were related to the B-cell developmental stage at which the tumors arose. However, the pattern of hypomethylated IAP loci in normal plasma cells (terminally differentiated B-cells) was more like that in normal LPS-stimulated B- cells than that in plasmacytomas. Messenger RNAs for enzymes that require S-adenosylmethionine (SAM) as substrate were quantitated to examine a possible effect of competition for SAM on DNA methylation. Levels of mRNA encoding ornithine decarboxylase, SAM decarboxylase, and methyltransferase did not correlate with the degree of IAP sequence hypomethylation observed in the various cells. In addition, hypomethylation of IAP loci did not correlate with genomic DNA hypomethylation in B-cells or B-cell tumors other than plasmacytomas. Thus, in some cells the hypomethylated IAP elements may serve as reporters of hypomethylation of selective genomic regions.
