Chromatin states sometimes captured differences in RNA expression that are missed by DNA methylation or accessibility. For example, TxFlnk, Enh, TssBiv, and BivFlnk states show similar distributions of DNA accessibility but widely differing enrichments for expressed genes (Fig. 4c,d). Enh and ReprPC states show intermediate DNA methylation, but very different distributions of DNA accessibility and different enrichments for expressed genes (Fig. 4c-e). Lack of DNA methylation, typically associated with de-repression, is associated with both the active TssA promoter state and the bivalent TssBiv and BivFlnk states. Bivalent states TssBiv and BivFlnk also showed overall lower DNA methylation and higher DNA accessibility than enhancer states Enh and EnhG and binding by both activating and repressive regulatory factors (Extended Data 2b). These results also held for alternate methylation measurement platforms (Extended Data 4a-c), and for the 18-state chromatin state model (Extended Data 4d-e). Overall, these results highlight the complex relationship between DNA methylation, DNA accessibility, and RNA transcription and the value of interpreting DNA methylation and DNA accessibility in the context of integrated chromatin states that better distinguish active and repressed regions.
