Figure 5 from A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer

Analysis of chromatin regulation by RMC-9945. A, Heatmaps and ATAC profile plots of differential peaks for vehicle-treated (n = 4,148) and RMC-9945–treated (n = 898) AKTP MTOs for 48 hours. B, Motif analysis on differential peaks reveals enrichment in members of the JUN/FOS family of TFs for vehicle (left) and LEF/TCF7 family of TFs for RMC-9945 (right). Top 30 significant most enriched motifs are shown. C, Representation (Gaudí plot) for ATAC-seq signal rendered for both the vehicle (left) and RMC-9945 (right), centered at chr6:134,835,000-135,835,000. Emp1 locus highlighted (green dot). All genomic bins within the dashed circle are taken into consideration for the motif search analysis. D, ChromBPNet contribution tracks for vehicle and RMC-9945 highlighting three (of six) AP1 motifs open in vehicle and closed in RMC-9945. Arcs represent the interaction between the TSS containing 5 kbp bin and those in spatial proximity in the Gaudí plot (dashed circle in C). E, Gaudí plot for ATAC-seq signal rendered for Lgr5 locus, centered at chr10:114,920,000-115,925,000. Same representation as in C. F, ChromBPNet contribution and interaction tracks for vehicle and RMC-9945 highlighting four (of five) TCF7/LEF1 TF-binding sites open in RMC-9945.