Figure 7. BETs primarily affect cardiac non-myocyte gene expression programs.

(A) Experimental protocol (n = 3 mice/treatment group). Non-myocytes: (B) Differentially expressed genes from pooled cardiac non-myocytes (relative to WT vehicle-treated mice) were predominantly downregulated in WT JQ1-treated mice and upregulated in PLN^R9C vehicle-treated mice. Non-myocytes from PLN^R9C mice treated with JQ1 displayed a marked shift in gene expression. (C) Pathways enriched in non-myocytes from PLN^R9C vehicle-treated mice with Z score ±2 were all downregulated or not enriched in mice treated with JQ1. Data represent the Z score versus WT vehicle-treated mice. (D) JQ1 treatment shifted gene expression in these pathways from predominantly up- to predominantly downregulated. Cardiomyocytes: (E) The pattern of differentially expressed genes from pooled cardiomyocytes (relative to WT vehicle-treated mice) was similar in PLN^R9C vehicle-treated and JQ1-treated mice. Further, JQ1 had virtually no effect on gene expression in WT cardiomyocytes. (F) Heat map of genes differentially expressed in PLN^R9C vehicle-treated cardiomyocytes showing little to no change in expression levels with JQ1 treatment. Data plotted are natural log of fold change values versus WT vehicle-treated mice.