To capture the greater complexity afforded by additional marks, we learned additional chromatin state models in subsets of cell types. In the subset of 98 reference epigenomes that also included H3K27ac data, we also learned an 18-state model (Extended Data 2c, Table S3b), enabling us to distinguish enhancer states containing strong H3K27ac signal (EnhA1, EnhA2), which showed higher DNA accessibility (Extended Data 3a), lower methylation (Extended Data 3b), and higher TF binding (Extended Data 2c) than enhancers lacking H3K27ac. In a subset of 7 epigenomes with an average of 24 epigenomic marks, we learned separate 50-state chromatin state models based on all the available histone marks and DNA accessibility in each epigenome (Fig. S4), which additionally distinguished: a DNase-state with distinct TF binding enrichments (Fig. S4f), including for mediator/cohesin components42 (even though CTCF was not included as an input track to learn the model) and repressor NRSF; transcribed states showing H3K79me1 and H3K79me2 and associated with the 5’ ends of genes and introns; and a large number of putative regulatory and neighboring regions showing diverse acetylation marks even in absence of the H3K4 methylation signatures characteristic of enhancer and promoter regions.
