“…For instance, candidate tissue-specific enhancers were found to be significantly enriched ( P -value ≤0.05, Fisher’s exact test) in binding sites for TFs within regulatory networks that are known to be important in the respective tissues, such as MYC and NFKB1 in heart, and HNF4A and SP1 in liver [46-49] (data not shown). The combined collection of enhancers predicted in the loci of the 200 most highly expressed genes in each of the tissues considered significantly overlap with ORegAnno, a manually curated collection of regulatory sequences [50], featuring a two-fold enrichment ( P -value <0.001, computed based on 1,000 randomized sequences genome-wide). Also, our enhancer predictions are enriched for specific epigenetic histone marks generally associated with distal transcriptional regulation, as suggested by 41% of predicted enhancers overlapping ChromHMM predictions for strong and weak enhancers (1.5-fold enrichment, P -value <0.001, computed based on 1,000 randomized sequences genome-wide [51]).…”