Figure 4. Delayed/impaired expression of developmental regulators in differentiating Tip60^ci/ci ESCs.

(A) Heatmap indicating induction kinetics of each germ layer markers during differentiation of Tip60^fl/+ controls or Tip60^ci/ci mutant ESCs. (B) K-means clustering (K = 9) of differentially expressed genes [|log2 (fold change)| > 0.7; multiple testing-adjusted p value < 0.05] in Tip60^fl/+ controls or Tip60^ci/ci mutant ESCs during the differentiation time course. Large up-regulated clusters are noted. Key regulatory proteins with impaired induction in Tip60^ci/ci mutant ESCs are highlighted. (C) Western blots (one of two independent experiments with similar results) of phosphorylated and total Smad2/3 and Erk1/2 during differentiation in Tip60^fl/+ or Tip60^ci/ci ESCs. (D) Model indicating the KAT-independent role of Tip60 in ESC self-renewal and gene regulation, as well as pre-implantation development, and the KAT-dependent role of Tip60 in differentiation and post-implantation development. See text for additional details.