Members of the L1 transposon family (long interspersed repeat DNA or LINE family) of rats are 6.7 kb long, 5 kb of which is devoted to protein encoding sequence (ORFs). A 610 bp CpG-rich sequence is at the left end of the element, and a guanine-rich polypurine:polypyrimidine sequence is near the right end. Although the protein encoding sequences of mammalian L1 families are highly conserved, the promoter sequences are completely distinct. This means that these families have ben independently amplified in various mammalian species. Our recent identification of a highly repeated murine ancestral L1 family indicates that L1 amplification has occurred repeatedly during mammalian evolution. Our previous demonstration that the rat L1 family contains an active regulatory region was the first evidence that L1 regulatory region and found that it contains three regions that can form specific DNA:protein complexes with nuclear extracts as judged by gel retardation experiments. Deletion analysis shows that the first region binds a transcriptional inhibitory factor while the third region binds a stimulatory factor. We also have found that the L1 regulatory region enhances the activity of regulatory sequences that are located 5' to it. In addition to activating cryptic promoters it also strongly stimulates both the early and late SV40 promoters. We previously showed that the L1 guanine-rich polypurine:polypyrimidine sequence destabilizes contiguous duplex DNA, adopts several non-B DNA structures in vitro. and that the L1 non-B structures compete with target site non-B structures for supercoil energy which in vivo might modulate the supercoil dependent properties of L1 elements and their target sites. In examining the effects of the L1 polypurine:polypyrimidine region in vivo, we now find that this region decreases the replication of plasmids bearing the SV40 replicon and alters the apparent activity of certain eukaryotic promoters. In parallel studies we have shown that homoguanine stretches enhance the mutation rate of adjacent DNA sequences in vivo.
