Mechanisms Regulating Stemness and Differentiation in Embryonal Carcinoma Cells

Figure 3

Global methylation and acetylation pattern of ECC lines during stemness and differentiation. Pluripotent ECCs are methylated and deacetylated yielding a low expression profile of differentiation markers. The dimerization of Jun Dimerization Protein 2 (JDP2) results in the recruitment of Histone Deacetylase 3 (HDAC3), which interacts and inhibits Histone Acetylases (HATs) from activating differentiation genes. Pluripotency is lost when DNA methyltransferase 1 (Dnmt1) expression and activity is reduced, resulting in the demethylation of differentiation-inducing genes including Vimentin, Laminin B1, Collagen IV, and Endo A. Similarly, HDAC activity is reduced as the p300 complex displaces the JDP2/HDAC3 complex, resulting in the recruitment of HATs and initiation of c-Jun transcription leading to differentiation.