Capturing drug responses by quantitative promoter activity profiling

Quantitative analysis of cellular responses to drugs is of major interests in pharmaceutical research. Microarray technologies have been widely used to monitor their changes at genome-wide scale, however it has several limitations in terms of coverage of targeted RNAs, sensitivity, and quantitativeness. In this article, we report an application of genome-wide and quantitative profiling of cellular responses to drugs at promoter level. We monitored promoter activities by Cap Analysis of Gene Expression (CAGE) employing a single-molecule sequencer. We identified a distinct set of promoters affected even by weakly inhibiting the Ras-ERK and PI3K-Akt signal-transduction pathways whereas corresponding differentially expressed genes were limited to be captured in the microarray analysis. Further, promoter responses to inhibition of the upstream EGFR kinase are explained by corresponding promoter activity for the two inhibitions, demonstrating enhanced utility of highly quantitative promoter activity profiling in drug research.