Assessing the variability across individuals and tissues is more difficult for enhancers than for gene expression (32). Not only is the variability in chromatin-mark level at enhancers across different individuals and tissues high, but the boundaries of enhancers can grow and shrink, sometimes disappearing altogether (e.g., for H3K27ac) (Fig. 3A). To investigate this in more detail, we uniformly processed the H3K27ac data from the PFC, temporal cortex (TC), and cerebellum (CB) on a cohort of 50 individuals, primarily of European descent and sequenced to similar depths (21) (fig. S24). Aggregating data across the cohort resulted in a total of 37,761 H3K27ac “peaks” (enriched regions) in the PFC, 42,683 in the TC, and 26,631 in the CB—where each peak is present in more than half of the individuals surveyed. In a comparison of aggregated sets for these three brain regions, the PFC was more similar to the TC than the CB (~90% versus 34% overlap in peaks). This difference is consistent with previous reports and suggests potentially different cell-type composition in the CB and the cortex (33, 34).
