Transposable element derived DNaseI-hypersensitive sites in the human genome

• Main Authors: Jordan I King, Mariño-Ramírez Leonardo
• Format: Article
• Language: English
• Published: BMC 2006-07-01
• Series: Biology Direct
• Online Access: http://www.biology-direct.com/content/1/1/20

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p> <p>Reviewers</p> <p>This article was reviewed by Wolfgang J. Miller (nominated by Jerzy Jurka), Itai Yanai and Mikhail S.Gelfand.</p>