Fig. 6

Poised mesenchymal promoters in treatment naive epithelial cells. a Chip-seq analysis for H3K4me3 in HN120 naïve, resistant and drug-holiday models. H3K4me3 marks on promoters of cisplatin-induced genes associated with cellular-reprogramming (EMT) in HN120 cells. Clusters CP-1 and CP-2 represent poised promoters, whereas CP-3 is associated with closed promoters. b Median expression of cisplatin-dependent upregulated genes from HN120 cells in clusters 1–3 (from Fig. 6a). c Quantitation of H3K27ac signals on promoters of cisplatin-dependent up-regulated genes in clusters 1–3 (from Fig. 6a) b, c mean + s.d., Mann–Whitney U test, ***P < 0.0005, *P < 0.005, #non-significant). d ChIP-seq tracks of H3K4me3 and H3K27ac on VIM, IL6, and GAS6 promoters in HN120Pri naive and drug-resistant/holiday models. Note the gain of H3K27ac marks in PCR/PCRDH cells (green asterisks), compared to naive (red asterisks), on EMT-associated promoters (y-axis = 0–75 (VIM, GAS6), 0–25 (IL6)). e Venn-diagram representing differential H3K27ac peaks in drug-sensitive and drug-resistant HN120 cells. HOMER based discovery of de novo transcription factor motifs in differential H3K27ac peaks. Note the loss of SOX2 motif in the drug-resistant HN120PCR cells, and the enrichment for SOX9 binding sites in the de novo acetylated promoters/enhancers. f Proposed model for SOX2 and SOX9 interplay during stem cell switch. Our data suggests that SOX2 expression maintains the epithelia cell-state while the loss of SOX2 and a concomitant gain of SOX9 results in the activation of an EMT program in HN120 drug-resistant and metastatic tumor cells