Hierarchical clustering of enhancers by facet expression revealed a small subset of enhancers (241 or 247, defined by primary cell or tissue facets, respectively) expressed in the large majority of facets (Supplementary Text, Supplementary Figs 24 and 25, and Supplementary Tables 12 and 13). Compared to other enhancers, the ubiquitous (u-) enhancers are 8 times more likely to overlap CGIs and they are twice as conserved (Supplementary Fig. 26a-c). U-enhancers overlap typical chromatin enhancer marks but have higher H3K4me3 signal (Supplementary Fig. 26d). Although they produce significantly longer ncRNAs than other enhancers (median 530 nt, P<1.5e-8, Mann-Whitney U test), the transcripts remain predominantly (~78%) unspliced and significantly shorter (P<4.2e-18, Mann-Whitney U test) than mRNAs (Supplementary Fig. 27-28), do not share exons with known genes, and are exosome-sensitive (Supplementary Fig. 14b). Therefore, it is unlikely that these are novel mRNA promoters. They are also highly enriched for P300 and cohesin ChIP-seq peaks20 and RNAPII-mediated ChIA-PET signal21 compared to other enhancers (Supplementary Fig. 26d). These results suggest that u-enhancers comprise a small but distinct subset of enhancers, which likely has specific regulatory functions utilized by virtually every human cell.
