Our results show that position-specific sequence signals upstream of the transcription initiation sites and the production of small, uncapped, RNAs immediately downstream is present at both enhancers and mRNA promoters, suggesting similar mechanisms of initiation. Previous studies (e.g. refs. 10,34,35) suggested that promoters and enhancers differ in motif composition. This view is not supported by the larger FANTOM5 dataset. Instead, the differences reflect the local GC content since transcribed enhancers tend to harbor GC-poor motifs like non-CGI promoters. Features distinguishing enhancers from mRNA promoters are: i) enhancer RNAs are exosome-sensitive regardless of direction while (sense) mRNAs have a longer half-life than their antisense counterpart; ii) enhancer RNAs are short, unspliced, nuclear and non-polyadenylated and iii) enhancers have downstream pA and 5’ splice motif frequencies at genomic background level similar to antisense PROMPTs, while mRNAs are depleted of termination signals and enriched for 5’ splice sites 11,12.
