A number of the aberrant glioma super-enhancers functionally are linked to genes involved in NOTCH signaling including ASCL1, HES5, and NOTCH1 (Fig. 3e–g, Supplementary Data 2) that we also identified later in this study as having increased expression in mutant cells (Supplementary Table 5), further underscoring the link, perhaps mediated in part by super-enhancers, between H3.3 mutation and NOTCH signaling. This evidence concerns the gene HES5 and central nervous system cancer.