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    Transposable element derived DNaseI-hypersensitive sites in the human genome

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    Jordan_BMC_2006_001.pdf (521.0Kb)
    Date
    2006-07-20
    Author
    Mariño-Ramírez, Leonardo
    Jordan, I. King
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    Abstract
    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 genomewide mechanism for generating functionally relevant gene regulatory divergence between evolutionary lineages.
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    http://hdl.handle.net/1853/42105
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