Fig. 4: Ezh2 pharmacological inhibition with GSK-343 increases bivalent gene expression and enhances human monocyte homing and angiogenic functions in vitro.

Global changes in gene expression upon GSK-343 treatment versus vehicle treatment analyzed by mRNA-seq (a) in cultured human monocytes. Volcano plot shows upregulated (red) and downregulated (green) genes (combined data from three different donors, n = 3) considered as statistically significant with a Benjamini-Hochberg adjusted p-value < 0.05. Classification of GSK-343-induced genes according to promoter status (b). Heatmaps of all significantly upregulated bivalent genes identified by RNA-seq analysis in human monocytes after GSK-343 treatment (c). Data obtained from three independent donors (n = 3) are expressed in log2 (FPKM). Representative tracks of changes induced by GSK-343 treatment on select up- and downregulated genes in human monocytes (d). Representative Gene Ontology (GO) Biological Process categories significantly (Benjamini-Hochberg adjusted p-value < 0.05) enriched for GSK-343-induced bivalent genes in human monocytes. The bar graph represents the −log10 (Benjamini-Hochberg adjusted p-value), obtained from DAVID gene-enrichment in functional annotation terms after Fisher’s Exact test filled with the number of genes revealed by the analysis within the number of overall genes in each GO biological process category indicated in red (e).