The distribution of RNA species across segments is quite distinct, indicating that underlying biological activities are captured in the segmentation. Polyadenylated RNA is heavily enriched in gene bodies. Around promoters, there are short RNA species previously identified as promoter-associated short RNAs (PASRs) (Figure 5B)16,70. Similarly, DNA methylation shows marked distinctions between segments, recapitulating the known biology of predominantly unmethylated active promoters (TSS states) followed by methylated gene bodies42 (T state, Figure 5D). The two enhancer-enriched states show distinct patterns of DNA methylation, with the less active enhancer state (by H3K27ac/H3K4me1 levels) showing higher methylation. These states also have an excess of RNA elements without poly-A tails and methyl-cap RNA as assayed by CAGE sequences compared to matched intergenic controls, suggesting a specific transcriptional mode associated with active enhancers71. TFs also showed distinct distributions across the segments (Figure 5B). A striking pattern is the concentration of TFs in the TSS-associated state. The enhancers contain a different set of TFs. For example, in K562, the E state is enriched for binding by the proteins encoded by the EP300, FOS, FOSL1, GATA2, HDAC8,
