My group has established an experimental system to study epigenetic control of L1 retrotransposon reporters integrated de novo into human or mouse chromosomes. Using this tissue culture system, we are studying the mechanism of variegation and silencing of L1 reporters, newly inserted via a retrotransposition-dependent mechanism. We have also studied epigenetic control of L1 retrotransposons in situ in the human and mouse genomes, and the relationship between such control and L1 expression in various cells. These experiments, as a test of the "genome defense model", have shown that DNA methylation does not by itself account for exceptionally strong negative regulation of L1 transcription in somatic tissues.We have successfully sequenced and analyzed several full Serial Analysis of Gene Expression (SAGE) long-tag libraries to characterize global transcript levels, including those corresponding to repetitive and transposable elements, in somatic cells with altered epigenetic controls. The libraries completed to date include numerous transcripts that are differentially expressed at very high ratios. We are now identifying the differentially expressed transcripts and further characterizing how altered expression may be related to changed epigenetic control.