Genomic environments scale the activities of diverse core promoters

One model for how cells integrate cis-regulatory information is that different classes of core promoters respond specifically to certain genomic environments. We tested this model using a genome-integrated massively parallel reporter assay (MPRA) to measure the activity of hundreds of diverse core promoters at four genomic locations and, in a complementary experiment, six core promoters at thousands of genomic locations. While genomic locations had large effects on expression, the relative strengths of core promoters were preserved across locations regardless of promoter class, suggesting that their intrinsic activities are scaled by diverse genomic environments. The extent of scaling depends on the genomic location and the strength of the core promoter, but not on its class. Our results support a modular genome in which genomic environments scale the activities of core promoters. One Sentence SummaryGenomic environments have consistent effects on gene expression that depend on the strength, but not the class of core promoter.