Extended Data Fig. 7: MAPK dependence and conservation of Kras-regulated sites.

a, Growth of two separate TO-KrasG12D lines cultured in the presence or absence of doxycycline. b, H3K27ac ChIP-seq intensity after the indicated treatments at KrasG12D-dependent enhancers identified as described in Fig. 4. Treatments were performed with an AKT inhibitor (MK2206, 2.5 µM) or separate treatment with two different MEK inhibitors (Refametinib and PD0325901, each 500 nM) for 12 hours prior to ChIP-seq. P-values derived from a Kolmogorov–Smirnov test, two sided.****, p<1x10-5. c, ATAC-seq intensity in mCherrypos cells isolated from the indicated mice at sites of MAPK-dependent H3K27ac. P-values derived from a Kolmogorov–Smirnov test, two sided.****, p<1x10-5. d, Top five enriched TF motifs at open chromatin sites enriched in human ADM cells compared to normal ductal cells (hADMOPEN) identified by scATAC-seq. e-h, Top five enriched TF motifs at the following regions: (e) sites of open chromatin enriched in terminally differentiated normal ductal cells compared to PDLPs identified by ATAC-seq in mCherrypos cells in Klf5-KI mice (K-LOCKEDCLOSED sites), (f) sites of open chromatin enriched in normal ductal cells compared with PDA ductal cells in human samples identified by scATAC-seq (hPDACLOSED sites), (g) sites of increased H3K27ac upon KrasG12D depletion identified in TO-KrasG12D mPDA cells (KrasG12D-repessed sites), and (h) sites of open chromatin enriched in normal ductal cells compared with ADM cells in human samples identified by scATAC-seq (hADMCLOSED sites). i, Normalized mean ATAC-seq intensity signals in pancreatic and other lineages at TSS peaks to genes in the “cell cycle” KEGG pathway. Samples are as described in Fig. 4g.