Figure 6.

GCN5 Affects Multiple Components of the FGF Signaling Pathway and Activates Selective Targets during Early Differentiation

Top: the abnormal phenotype of Gcn5^−/− EBs becomes evident early during EB differentiation (day 5). Loss of Gcn5 leads to disorganization of the epiblast architecture that is associated with defective cytoskeleton networks (F-actin and vimentin) and decreases in progenitors fated for mesoderm. At later stages of differentiation (days 9 and 12), Gcn5^−/− EBs are smaller in size and express lower levels of marker genes for ectoderm (blue), endoderm (green), and mesoderm (magenta), compared with the controls. Lighter shades indicate decreased expression levels of marker genes for each population. Middle: at day 5, GCN5 affects expression of multiple genes encoding critical components in FGF signaling and for proper activation of ERK and p38 pathways. Solid diamond, up (red) or down (green) regulated transcripts; open diamond (green), decreased protein expression; double open diamond (green), decreased protein phosphorylation. Bottom: at day 5, GCN5 is required for activation of genes important for signaling through promoter-associated H3K9ac, including four cMYC targets (blue).