Fig. 7: KLF4 and RUNX1 are associated with liver-biased and lung-biased chromatin states.

a, ATAC-seq and RNA-seq combined scores for the indicated TF families in liver versus lung metastases. This metric infers the probability that a given TF family with a significantly enriched motif in the ATAC-open regions impacts SMAD4-induced gene expression changes on the basis of a consistent RNA-seq change in the Smad4 on versus off comparison (Methods). Top TF families scored using the HOMER de novo motif analysis in the liver versus lungs are shown. b, Combined scores for the indicated TF families in liver and lung metastases from PDAC patients40. This metric infers the activity of a given TF family on the basis of enrichment or depletion of its predicted target genes in the respective metastases versus primary tumors but not in the corresponding normal tissues (Methods). Top TFs scored using JASPAR or TRANSFAC position weight matrix data are shown. c, Representative IHC staining for KLF4 and RUNX1 in KC-shSmad4 (+Dox) liver or lung metastases. Right, higher-magnification views of the dashed areas to highlight tumor-specific nuclear signal. Data are representative of 20 metastases from four independent mice.