Fig. 3: Chromatin-focused genetic and chemical probe library screens reveal epigenetic vulnerabilities of Taxol-resistant TNBC cells.

a A schematic representation of EPIKOL screen on T1-160 resistant cells. Cells were infected with 1,000× representation of library with an MOI of 0.3 and selected with puromycin. After completion of Cas9 activity approximately 9 days after transduction, cells were divided into two groups as DMSO-treated and Taxol-treated (160 nM) groups. The final time-point samples were compared to identify epigenetic modifiers that sensitize Taxol-resistant cells. Created with BioRender.com. b Results of the EPIKOL screen performed on T1-160 cells, presented as LFC of genes in Taxol-treated samples compared with the DMSO-treated group. Genes that have P < 0.05 were colored and labeled. c A schematic representation of the epigenetic chemical probe library screen. Cells were seeded to 384-well plates at 750 cells per well and the next day treated with Taxol (parental: 1.5 nM, T1-160: 300 nM, T2-450: 500 nM) and 1× concentration of epigenetic probe library. After 3 days, cell viability was measured. Created with BioRender.com. d Results of the epigenetic probe library screen performed on T1-160 cells. The gray dots represent the effect of epigenetic probes alone, while the orange dots show changes in cell viability when Taxol was combined with a specific epigenetic probe. Epigenetic probes that significantly reversed drug resistance are labeled in the graph. If the negative control of a given probe also showed a significant depletion in cell viability, neither probe was labeled on the graph. e Classification of hits identified in genetic (left) and chemical (right) screens. For the chemical screen, the target genes of chemical probes are indicated in the outer circle.