This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The evolutionary origins and functional roles of human non-coding sequences, which make up the vast majority (~98.5%) of the genome, remain largely unknown. Many of these sequences are derived from transposable elements (TEs), and the aim of my research is to explore the contribution of TEs to regulatory sequences that control the expression of human genes. Our previous studies have shown that the remnants of numerous TE insertions have been coopted to provide several distinct classes of human regulatory sequences including cis-regulatory elements and scaffold/matrix attachment regions. Together with graduate student Jittima Piriyapongsa, I propose to further explore the relationship between TEs and human regulatory sequences with an emphasis on non-coding RNA regulatory sequences such as small interfering RNAs (siRNAs) and micro RNAs (miRNAs). We plan to use the Bioinformatics Resource at the Pittsburgh Supercomputing Center to aid in the construction high resolution genomic maps that combine the locations of human non-coding RNA regulatory sequences and their targets, characterized by recently developed high throughput experimental techniques, with TE sequence positions. These maps will then be employed in cross-species comparisons, across different levels of evolutionary relatedness, in an attempt to characterize the evolutionary dynamics of TE-derived non-coding RNA regulatory sequences. Finally, patterns of gene expression will be used in efforts to discern the particular regulatory effects exerted on target genes by TE-derived non-coding RNAs, and where possible, to explore evolutionary changes in expression wrought by lineage-specific insertions of TE regulatory sequences.
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