Gene expression in mammals is precisely regulated by the combination of 
promoters and gene-distal regulatory regions, known as enhancers. Several 
studies have suggested that some promoters might have 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 the 
involvement of these promoters in the cis regulation of expression of distal 
genes in their natural loci. Our results have important implications for the 
understanding of complex gene regulation in normal development and disease.