Figure 8. NF-κB is activated in a BRD4-dependent manner in PLN^R9C hearts.

(A) Heat map of genes known to be activated by NF-κB demonstrated uniform upregulation in cardiac non-myocytes, with a majority of genes being switched off by JQ1 therapy. Data plotted are natural log of fold change values versus WT vehicle-treated mice. GSEA for genes induced (B) in vehicle-treated or attenuated (C) in PLN^R9C JQ1-treated mice against a curated set of genes known to be directly induced by NF-κB. (D) Western blot showing increased aK310-RELA in PLN^R9C compared with WT hearts irrespective of JQ1 treatment status (representative images of n = 3 experiments). Boxes show IQR and whiskers, 1.5× IQR; individual data points are plotted. Student’s 2-tailed t test. (E) Western blots (IB) from the co-IP of BRD4 with anti-BRD4, anti-RELA, and anti–ak310-RELA demonstrated direct binding of BRD4 and NF-κB in PLN^R9C hearts with DCM. This was completely ablated by treatment with JQ1 (representative images of n = 3 experiments).