Figure 7
Loss of Topors confers a gene expression profile similar to histone deacetylase inhibition and resistance to trichostatin A. A. From a collection of 453 gene expression profiles representing 164 compounds, the expression profiles of the histone deacetylase inhibitors HC toxin, trichostatin A, and vorinostat are highly similar to the gene expression profile of murine embryonic fibroblasts lacking Topors. The barview (left) is constructed from 453 horizontal lines, each representing an individual treatment instance and ordered by their similarity to the Topors signature. All HC toxin (n = 1), trichostatin (n = 12), and vorinostat (n = 2) instances are shown as black lines. Colors applied to the remaining instances reflect positive (green), negative (red), or no (gray) similarity to the Topors signature. The table shows the rank, dose, cell line, and connectivity score for each histone deacetylase inhibitor treatment instance. B. Topors+/+ (solid lines) and Topors-/- (dotted lines) MEFs were incubated for 72 hours with increasing concentrations of trichostatin A. Anti-proliferative activity was determined using an MTT assay. Data represent means and standard deviations of 3-6 replicates. Estimated IC50 values for trichostatin A are 30 ng/ml for Topors+/+ cells versus 232 ng/ml for Topors-/- cells (P < 0.0001, F test).