High resolution discovery of regulatory DNA with synthetic wild-type and ablated genome constructs

Genomic enhancer elements play a role in modulating gene expression by interacting with effector proteins known as transcription factors. We present a new computational method, "STARR-scan", which identifies transcription factor motif appearances in synthetic DNA constructs that are correlated with enhancer activity. Using a tiled STARR-seq assay, we demonstrate that STARR-scan can suggest the biological function of transcription factors previously suspected to activate the APOBEC-3B gene. Using the same methodology, STARR-scan can suggest transcription factors with previously unknown biological activity which may regulate the APOBEC-3B gene. These novel factors may have biological significance in our understanding of cancer biology.