TRANSPOSABLE ELEMENT DERIVED NON-CODING RNA REGULATORY SEQUENCES IN THE HUMAN G

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 人类非编码序列占基因组的绝大多数（约98.5%），其进化起源和功能作用在很大程度上仍然未知。这些序列中有许多来自转座因子（TE），我的研究目的是探索TE对控制人类基因表达的调控序列的贡献。我们以前的研究已经表明，许多TE插入的残余物已被增选，以提供几个不同类别的人类调控序列，包括顺式调控元件和支架/基质附着区。与研究生Jittima Piriyapongsa一起，我建议进一步探索TE与人类调控序列之间的关系，重点是非编码RNA调控序列，如小干扰RNA（siRNA）和微小RNA（miRNA）。我们计划使用匹兹堡超级计算中心的生物信息学资源来帮助构建高分辨率基因组图谱，该图谱将人类非编码RNA调控序列及其靶标的位置与TE序列位置相结合，其特征在于最近开发的高通量实验技术。这些地图，然后将采用跨物种的比较，在不同层次的进化相关性，试图表征TE衍生的非编码RNA调控序列的进化动力学。最后，基因表达的模式将被用于努力辨别TE衍生的非编码RNA对靶基因施加的特定调控作用，并在可能的情况下，探索TE调控序列的谱系特异性插入所引起的表达的进化变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.