In this manuscript, we focus on a subset of 1,936 datasets (Fig. 2) comprising 111 reference epigenomes (Fig. 2a-d), which we define as having a core set of five histone modification marks (Fig. 2e). The five marks consist of: H3K4me3, associated with promoter regions10,24; H3K4me1, associated with enhancer regions10; H3K36me3, associated with transcribed regions; H3K27me3, associated with Polycomb repression25; and H3K9me3, associated with heterochromatin regions26. Selected epigenomes also contain a subset of additional epigenomic marks, including: acetylation marks H3K27ac and H3K9ac, associated with increased activation of enhancer and promoter regions27-29 (Fig. 2f); DNase hypersensitivity7,18, denoting regions of accessible chromatin commonly associated with regulator binding (Fig. 2g); DNA methylation, typically associated with repressed regulatory regions or active gene transcripts4,30 and profiled using whole-genome bisulfite sequencing (WGBS)19, reduced-representation bisulfite sequencing (RRBS)20, and mCRF-combined31 methylation-sensitive restriction enzyme(MRE)22 and immuno-precipitation based21 assays (Fig. 2h); and RNA expression levels8, measured using RNA-seq and gene expression microarrays (Fig. 2i). Our definition of 111 reference epigenomes is very similar to that used by the International Human Epigenome Consortium (IHEC), which required RNA-seq, WGBS, and H3K27ac that are
