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

Figure 6.

Figure 6

Specific inhibition of H3K27ac at ER target genes by A-485. (A) A-485 reduces H3K27ac intensity at the genes downregulated by A-485 in MCF-7 cells. (B) A-485 specifically reduces H3K27ac levels at estrogen-regulated genes that are repressed by A-485. The estrogen-regulated genes are from the members of the GSEA Estrogen Early Hallmark Gene Set. (C) A-485 reduces H3K27ac at active enhancers associated with transcriptionally downregulated genes identified in the microarray dataset (Figure 4A) in MCF-7 cells. (D,E) A UCSC genome browser track for the MYC (D) or CCND1 (E) locus. A-485 reduces H3K27ac at the MYC promoter and an ER-responsive upstream enhancer (D), while inhibiting H3K27ac at a CCND1 ER-responsive downstream enhancer (E) in MCF-7 cells. (F) Fold changes of H3K27ac intensity of ChIP-seq peaks associated with the MYC promoter (Promoter Peak 1 and Peak 2), MYC Enhancer, and CCND1 enhancer. (G) Validation of A-485-mediated inhibition of H3K27ac at the MYC promoter, MYC enhancer and CCND1 enhancer in MCF-7 cells, as measured by ChIP-qPCR (n = 2). *: p < 0.05; **: p < 0.005; *** p < 0.0005 (Poisson regression model by HomeR in panel F and Student’s t-test in panel G).