BACKGROUND: Transposable elements (TEs) are abundant genomic sequences that have 
been found to contribute to genome evolution in unexpected ways. Here, we 
characterize the evolutionary and functional characteristics of TE-derived human 
genome regulatory sequences uncovered by the high throughput mapping of 
DNaseI-hypersensitive (HS) sites.
RESULTS: Human genome TEs were found to contribute substantially to HS 
regulatory sequences characterized in CD4+ T cells: 23% of HS sites contain 
TE-derived sequences. While HS sites are far more evolutionarily conserved than 
non HS sites in the human genome, consistent with their functional importance, 
TE-derived HS sites are highly divergent. Nevertheless, TE-derived HS sites were 
shown to be functionally relevant in terms of driving gene expression in CD4+ T 
cells. Genes involved in immune response are statistically over-represented 
among genes with TE-derived HS sites. A number of genes with both TE-derived HS 
sites and immune tissue related expression patterns were found to encode 
proteins involved in immune response such as T cell specific receptor antigens 
and secreted cytokines as well as proteins with clinical relevance to HIV and 
cancer. Genes with TE-derived HS sites have higher average levels of sequence 
and expression divergence between human and mouse orthologs compared to genes 
with non TE-derived HS sites.
CONCLUSION: The results reported here support the notion that TEs provide a 
specific genome-wide mechanism for generating functionally relevant gene 
regulatory divergence between evolutionary lineages.
REVIEWERS: This article was reviewed by Wolfgang J. Miller (nominated by Jerzy 
Jurka), Itai Yanai and Mikhail S.Gelfand.