Protein-coding gene promoters more often overlapped CSs associated with active, weak or inactive/poised promoters, and were also more strongly enriched for Polycomb-repressed regions. Relative to protein-coding gene promoters, those of lncRNA genes more often overlapped CSs associated with insulators, regions of transcriptional transition (regions located between the initiation and elongation histone marks), elongation, weak transcription and heterochromatin (Figure S3, Table S3). After the subsets of lncRNA and protein-coding genes with similar expression levels in different cell lines were selected (see Methods), the same tendency remains but the difference between the promoters of protein-coding and lncRNA genes becomes less pronounced (Figure S5, Table S6). The role for enhancer-associated lncRNAs in regulating protein-coding genes over large genomic distances was recently reported [49]. Our data shows that in genes with non-zero similar expression levels most of the enhancer states are overrepresented in lncRNAs vs protein-coding genes (Figure S5), while in six out of eight studied cell types for all (independent of the expression levels) promoters only one out of four enhancer-associated CSs (weak enhancers) displays significant overrepresentation at lncRNA versus protein-coding gene promoters (Text S1 Results section).
