Prediction and Identification of Transcriptional Regulatory Elements at the Lung Cancer-specific Locus

The glycoprotein dickkopf 1 (DKK1) is highly expressed in lung cancer cell lines and tissues. Our previous study demonstrated that promoter activity is low in lung cancer cell lines. This may be because it lacks the necessary transcriptional regulatory elements (TREs) required for higher activity levels. However, it is difficult to computationally predict functionally significant TREs, as TREs from different locations can affect large segments of distant DNA. The Encyclopedia of DNA Elements project features multiple integrated technologies and approaches for the discovery and definition of functional elements, including enhancer elements and enhancer-blocking insulators. In the present study, DNase I hypersensitive sites and histone modifications of were investigated in the A549 lung cancer cell line using the UCSC Genome Browser. A set of cis-acting enhancer elements were identified by a dual-luciferase reporter gene assay system to increase activity of the promoter with lung cancer specificity. To the best of our knowledge, these data provide the first insight into the role of the locus in lung cancer, and confirm the contribution of intronic cis-acting elements to the regulation of expression, providing a new insight into gene regulation in lung cancer, which could inform the development of targeted therapy.