Fig. 3

JQ1 and BRD4 knock-down converge on Myc and AP1 to attenuate cytoskeleton related genes. An additional dataset comprising IMR90, Human airway fibroblasts, under conditions of quiescence or growth and stimulated with DMSO, JQ1, control shRNA, or shBRD4. Pattern analysis was performed to identify JQ1 sensitive and BRD4 sensitive DEGs defined as those that were perturbed by growth conditions and attenuated to near baseline, quiescent levels with JQ1 or shBRD4. A A Venn diagram illustrating the extent of shared DEGs that were sensitive to both JQ1 and shBRD4. B Genes from each group in the Venn diagram; attenuated only by JQ1, attenuated only by shBRD4, and those attenuated by both were subjected to TF enrichment analysis with ChEA3 using the ENCODE, ChIP-seq database of TF-gene interactions was used to identify TFs implicated in regulated each group of genes. TFs were rank-ordered by the –log10 of the Fisher’s Exact Test (FET) value. C Normalized counts of relevant TFs implicated in the TF enrichment analysis, TFs implicated in previously published findings as well as bromodomains were plotted. Each plot contains the average expression of DMSO-stimulated quiescent cells (Ctrl_Qsnt), DMSO or shRNA control stimulated proliferative cells (Ctrl_Pro), and JQ1 or shBRD4 stimulated proliferative cells (Expt_Pro) in pink and blue respectively. JQ1 attenuated DEGs and shBRD4 attenuated DEGs were separated between up regulated and down regulated genes (based on their expression in JQ1 and shBRD4 proliferative cells compared to the proliferative control cells). The down regulated, JQ1 and shBRD4 genes were subjected to active subnetwork searches to BIOGRID protein–protein interaction network and subsequent enrichment analysis using GO terms for cellular compartment with the pathfindR package. D The shared and uniquely enriched terms between the shBRD4 (BRD4) attenuated DEGs and the JQ1 attenuated DEGs were plotted in a dotplot. Each dot reflects an enriched term, the x-axis reflects the fold enrichment of each term, the color of each dot corresponds to the –log10 of the adjusted p-value which is adjusted based on Bonferroni method and the size of each dot corresponds to the number of genes from the DEG lists associated with each term. Cytoskeleton associated terms sensitive to both JQ1 and BRD4 knock-down are highlighted with green rectangles