Gene regulation in the human genome is controlled by distal enhancers that activate specific nearby promoters. One model for this specificity is that promoters might have sequence-encoded preferences for certain enhancers, for example mediated by interacting sets of transcription factors or cofactors. This “biochemical compatibility” model has been supported by observations at individual human promoters and by genome-wide measurements in.
Here we designed a high-throughput reporter assay called ExP STARR-seq and applied it to examine the combinatorial compatibilities of 1,000 enhancer and 1,000 promoter sequences in human K562 cells. We identify simple rules for enhancer-promoter compatibility: most enhancers activated all promoters by similar amounts, and intrinsic enhancer and promoter activities combine multiplicatively to determine RNA output .
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