Genome-wide characterization of mammalian promoters with distal enhancer functions

Gene expression in mammals is precisely regulated by combination of promoters and gene-distal regulatory regions, known as enhancers. Several studies have suggested that some promoters might play enhancer functions. However, the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive. Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene-promoters. Extensive CRISPR/Cas9 genomic manipulation demonstrated their involvement in cis-regulation of distal gene expression in their natural loci. Our results have important implications for the understanding of complex gene regulation in normal development and disease. Overall design: CapStarr-seq analysis of DnaseI regions in K562 and HeLa cell lines (2 replicates) and in the plasmid library before transfection (Input).