Fig. 4
From: Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival
BRD4 occupies catabolic genes regulatory regions in cachexia and its recruitment is impaired by JQ1 administration. a Scatter plot of log10 fold changes between BRD4cachexia and BRD4ctrl vs. fold changes between BRD4cachexia+JQ1 and BRD4cachexia for all enriched regions. The negative slope indicates the inhibitory effect of (+)-JQ1 on BRD4 occupancy reversing the cachexia effect on BRD4 occupancy. b Pie chart showing BRD4 distribution in control skeletal muscle (left panel) and cachectic muscles vs. control (right panel). c Selected functional categories of genes with higher BRD4 in skeletal muscle of (−)-JQ1-treated C26-tumor-bearing mice vs. control muscles (top panel) and in muscles from (−)-JQ1 vs. JQ1(+)-treated C26-tumor-bearing mice (bottom panel). d–f BRD4 ChIP-seq tracks of Trim63 (MuRF1), Fbxo32 (Atrogin1/MAFbx), and GABARAPL1 loci. Bottom to top: input, control muscles, muscles from C26-tumor-bearing mice treated with (+)-JQ1 and (−)-JQ1 (top). g RNAPolII ChIP qPCR at promoters of muscle catabolic genes. Beta globin gene was used as a negative control. IgG was used as a reference. n = 3.Statistical analysis was performed by using one-way ANOVA followed by Tukey’s post hoc test. Data represent means ± SEM. *p < 0.05; **p < 0.01. “a” indicates statistical significance compared to control; “b” indicates statistical significance compared to C26 + (−)-JQ1 20 mg/kg/day
