The LTRs of expressed IAP elements show variations in sequence, and contain at least five binding sites for nuclear factors. Expression requires hypomethylation of the 5' LTR regulatory regions. Thus, expressed IAP elements are an indicator of the methylation status of their location in the genome and also reflect the presence and balance of particular factors. A limited and highly characteristic set of IAP elements (designated LS-elements) is expressed in normal mouse B-cells (Kuff AR 91). Plasmacytomas generally express higher levels of RNA. We characterized the IAP elements expressed in plasmacytoma MPC11 by sequence analysis of 22 cDNA clones. While the LTRs of the tumor cDNAs were all highly related by sequence, none of the clones were of the LS type (Lueders AR 92). The MPC11 LTRs were 5 to 6-fold more active than an LS cDNA LTR when tested for promoter activity after transfection into S194 plasmacytoma cells. We observed that the tumor-derived cDNAs differed from the LS cDNAs in the sequence of an ATF site; the MPC11 LTRs contain a canonical core sequence TGACGTCA (ATF-PC) while the LS cDNAs contain an altered sequence (ATF-LS). Nuclear extracts from S194 cells reacted at much lower concentrations in gel shift assays with an ATF-PC oligonucleotide than with an ATF-LS probe. The ATF-PC probe detected multiple IAP transcripts in RNA from established plasmacytomas, but gave no reaction with B-lymphocyte RNA. In contrast, ATF-LS detected higher levels of IAP transcripts in lymphocyte than in tumor RNAs. The results indicate that expression of IAP elements in transformed B-cells is selective for a different set of regulatory sequence variants than those expressed in normal B-cells.
