Smad4 directly binds to cell cycle genes downregulated upon re-expression of SMAD4. (A) Smad4 binding sites from mouse whole epithelium (n = 2), or CaCo2 (n = 1) and SW480 (n = 1) human CRC cells. ChIP-Seq data are compared with significantly regulated genes from RNA-Seq of tumor organoids +/− SMAD4 (from Figure 6, log2FC > 1 or <−1, adj p-value < 0.05). (B) DAVID analysis of genes directly bound by SMAD4 and upregulated and (C) downregulated. (D) RNA-Seq of cell cycle genes bound by SMAD4 and significantly downregulated (adj p-value < 0.05). (E) IGV of cell cycle genes in SMAD4 ChIP-Seq from mouse epithelium (n = 2, blue), SW480 (red), and CaCo2 (green).