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. 2021 Jun 4;13(11):2799. doi: 10.3390/cancers13112799

Figure 3.

Figure 3

p300 is critical for the expression of estrogen-regulated genes in MCF-7 cells. (A) A-485 downregulates expression of estrogen-regulated genes in MCF-7 cells. Global gene expression in MCF-7 cells treated with A-485 (3 µM) for 24 h was analyzed using microarray. A-485 upregulates 141 genes (FC ≥ 1.25, p < 0.05) and downregulates 142 genes (FC ≤ −1.25, p < 0.05). The downregulated genes were analyzed for their involvement in biological pathways using GSEA Hallmarks Gene Sets. The top statistically enriched pathways are shown (right). (B) Genetic depletion of EP300 via siRNA downregulates expression of estrogen-regulated genes in MCF-7 cells. The log2 FC of all differentially expressed genes (p < 0.05) are shown. The downregulated genes were analyzed for their involvement in biological pathways using GSEA Hallmarks Gene Sets. The top statistically enriched pathways are shown (right). (C) CBP/p300 KAT inhibitor A-485 and EP300 genetic depletion impair ER signaling similarly. The genes repressed by A-485 in (A) were compared to the genes downregulated by EP300 genetic depletion (B). Genes downregulated by both were analyzed for their involvement in biological pathways using GSEA Hallmarks Gene Sets. The top statistically enriched pathways are shown below. (D) Members of the GSEA Estrogen Early Hallmark Gene Set downregulated by both A-485 and EP300 genetic depletion are shown with their respective fold changes.