Fig. 1.

—Defining the enhancers analyzed in this study. We analyzed enhancers previously identified in primary liver tissue from ten mammals (Villar etal. 2015). Enhancers were defined on the basis of histone modifications (presence of H3K27ac peaks, absence of H3K4me3 peak). We analyzed sequences alignable across all ten species to disentangle sequence conservation from regulatory activity conservation across species. To identify trends that would hold across all mammals, we restricted our analysis to extremes of the activity conservation spectrum: conserved-activity enhancers (green), and species-specific-activity enhancers (red). We considered species-specific-activity enhancers from human, mouse, cow, and dog to represent a diverse array of clades.