In this paper, we use this resource to gain insights into the epigenomic landscape, its dynamics across cell types, tissues, and development, and its regulatory circuitry. We find that combinations of histone modification marks are highly informative of the methylation and accessibility levels of different genomic regions, while the converse is not always true. Genomic regions vary greatly in their association with active marks, with approximately 5% of each epigenome marked by enhancer or promoter signatures on average, which show increased association with expressed genes, and increased evolutionary conservation, while two thirds of each reference epigenome on average are quiescent, and enriched in gene-poor and nuclear lamina-associated stably-repressed regions. Even though promoter and transcription associated marks are less dynamic than enhancer mark, each mark recovers biologically-meaningful cell type groupings when evaluated in relevant chromatin states, allowing a data-driven approach to learn relationships between cell types, tissues, and lineages. The coordinated activity patterns of enhancer regions enable us to cluster them into co-regulated modules, which are proximal to genes with common functions and phenotypes and enriched in regulatory motifs, enabling us to predict candidate upstream regulators.
