a, Network depiction of the conserved enhancer regulatory transcription factor network in the MM1.S cell line. TF nodes are denoted, and predicted binding interactions with super-enhancers driving other TFs are shown as lines (edges). Enhancer-regulated bHLH TFs are highlighted in orange. b, Histogram plot ranking core regulatory circuit TFs based on motif co-occupancy with MYC. c, Left axis, quantified mRNA levels of TCF3 upon shRNA-mediated knockdown in the MM.1S cell line. Right axis, corresponding viability defect observed upon TCF3 knockdown as measured by ATP levels. Shown is the average of three experiments performed in triplicate. d, Line plot of 3H thymidine uptake at days 1 and 3 after shRNA cell lines expressing selection for each respective shRNA in the MM.1S cell line. Thymidine uptake is shown normalized to day 1 levels. e, Bar plot of the fraction of live shRNA-expressing cells as measured by GFP positivity. Data are represented as fold change as compared to day 1 after infection. f, Percentage of early (Annexin V) and late (Annexin V and DAPI) apoptotic and live (unstained) cells four days after shRNA infection in the MM.1S cell line. The MM1.S cell line (left) and U266 cell line (right) are shown. g–j, Same as in c–f (respectively) in the U266 cell line.