Development of a Non-Restricted Functional Elements Assay Method for Identifying Genome-Wide Regulatory Elements

• Main Authors: Yi-An Ko, 柯怡安
• Other Authors: Qing-Dong Ling
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/80687887663950524729

碩士 === 國立中央大學 === 生物資訊與系統生物研究所 === 97 === A major challenge for post-genomics research is the integration gene expressions with their corresponding regulatory elements and chromatin architectures on a genome-wide scale. Regulatory elements exert diverse mechanisms to regulate the expression of genes through protein-protein or protein-DNA interactions, while chromatin structures act in the upstream of the regulatory cascade and have a broad effect on the expression of multiple genes. Here, we developed a novel method, denoted as genome-wide non-restricted functional elements assay (NOFEE), to identify changes of regulatory elements and to pursue a more comprehensive characterization of the gene expression profile of HCT-116 colorectal cancer cell line in response to the treatment of a Pt-based compound. Our experiments integrate high-resolution promoter tiling arrays and exon arrays on samples that were treated with optimized concentration of DNase I. Data were subsequently analyzed with ‘Partek’ software package, which is a commercial product based on pair-wise Gaussian merging method. A total of 12,117 regions in the promoter array and 3,043 differentially expressed genes in the exon array were used in our experiment. By integrating these datasets, we show that 61% of the exon expression profile can be associated with promoter regulatory regions suggesting that promoters in these regions may be directly involved in the transcriptional regulation of in response to Pt-compound treatment. Our results also suggest that the NOFEE approach can be a powerful method for genome-wide investigations of cis-acting regulatory elements.