In addition, we examined coordinated changes in chromatin marks associated with cellular differentiation56. We found that enhancers showing coordinated differences in multiple marks are enriched near genes showing common tissue-specific expression, and common knockout phenotypes based on their mouse orthologs. For example, enhancers that showed higher H3K27ac and H3K4me3 (Fig. 4i, Cluster C2) in left ventricle (E095) relative to their ESCs (E003) and mesendodermal (E004) precursor lineages were enriched for heart ventricle expression and cardiac and muscle phenotypes in their mouse orthologs.
