Fig. 3

Mapping of cis-regulatory circuits, units, and networks in tumor chromatin. a Method: Each of the sequenced methylation sites was assessed for association with the expression of the targeted genes across the tumor libraries. Theoretical positive and negative regulatory circuits are shown. b Fractions of the mapped positive or negative regulatory circuits. c Distributions of all, negative, or positive circuits per genes. d Distributions of all, negative, or positive units per gene. e A schematic map of regulatory sites and units that were associated with expression of the SMO driver-gene. f levels of SMO expression in GBM cells, following genomic deletion of unit “A” (an inferred enhancer) or of unit “D” (an inferred silencer), versus mock genomic targeting by scrambled targeting guides. g Levels of SMO expression in GBM cells lacking unit “D,” following genomic deletion of unit “A,” or mock targeting of unit “A,’ versus untreated cells