Fig. 4. BET bromodomain inhibition suppresses transactivation of shared transcriptional networks across HF models. BET bromodomain inhibition suppresses.

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Fig. 4. BET bromodomain inhibition suppresses transactivation of shared transcriptional networks across HF models. BET bromodomain inhibition suppresses transactivation of shared transcriptional networks across HF models. (A) Venn diagram showing significant overlap of gene sets that are stress-induced and JQ1-suppressed across the TAC and MI models (χ2 < 0.001). A common set of 193 genes was identified as being shared targets of BET bromodomain inhibition (gene list is provided in table S4). (B) Gene ontology analysis using DAVID for the Venn overlap genes shown in (A). A false discovery rate (FDR) of <0.05 was considered statistically significant. (C and D) Ingenuity Pathway Analysis. The common gene set was analyzed by Ingenuity Pathway Analysis. These analyses revealed two dominant signaling networks that were highly enriched in the set of genes suppressed by JQ1. (C) A large TGF-β network (P < 1.0 × 10−76). Each target gene is shown in red, with the darkness of red shading designating the relative degree of inhibition by JQ1 of that particular gene. Although the legend includes a green color scale for JQ1–up-regulated genes, there are no green-shaded genes on this diagram because all genes were selected a priori to be those that are suppressed by JQ1. TGFB1 as a central node gene is shown in orange. (D) JQ1 suppressed genes enriched for a network of innate immune signaling nodes with strong convergence on NFκB transcriptional responses (P < 1.0 × 10−48). Keys for the Ingenuity Pathway Analysis color shading and line formatting schemes are provided in the figure. Qiming Duan et al., Sci Transl Med 2017;9:eaah5084 Published by AAAS