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. Author manuscript; available in PMC: 2016 Sep 14.
Published in final edited form as: Nat Chem Biol. 2016 Mar 14;12(5):317–323. doi: 10.1038/nchembio.2042

Figure 5. Characterization of COMET-mediated gene expression signatures in human cells.

Figure 5

BG14 induces a light dose and compound concentration-dependent change in gene transcription in MCF-7 cells that is highly correlated with the gene expression signature of class I HDAC inhibitors. Specific examples of light-dependent up- and down-regulation of the HDAC inhibitor responsive landmark genes PAK1 (a) and CDK2 (b) in the presence of varying concentrations of BG14 and varying light exposure (no light, 250ms/750ms on/off, 750ms/250ms on/off (470 nm, 8.5 mW/cm2, 1 Hz) for 1 6 h. Data points represent values of 4 independent biological replicates. (c) Heat map of top 100 up- and down- regulated transcripts (landmark and inferred genes) that were specifically modulated by BG14 in light-dependent fashion. No meaningful transcriptional changes were observed by BG14 treatment alone or by light in the absence of inhibitor (control, 1 μM, 5 μM, 25μM; data represent average of n=4 measurements). (d) Gene Set Enrichment Analysis (GSEA) confirms the strongly correlated transcriptional response of CI-994 and BG14 (25 μM, 470 nm, 8.5 mW/cm2, 1 Hz, 75% duty cycle, 1 6 h). p < 0.001 and FDR q < 0.001 (e) Venn diagram showing the overlap between CI-994 and C60 response genes and BG14 regulated light-dependent “on-target” and light-independent “off-target” genes, respectively.