FIGURE 6.

A summary of the regulation pathways/networks in U937 cell differentiation. Cell differentiation up-regulates the clathrin-mediated endocytosis pathway, resulting in overexpression of transforming growth factors as well as integrins that are required for cell morphology changes. Biotin uptake may also be elevated by endocytosis, resulting in increased biosynthesis of fatty acids and ceramides. Biotin is also required for the activation of propionyl-CoA carboxylase (PCC) to convert propionyl-CoA into methymalonyl-CoA, resulting in a decrease in histone H3 Lys-23 propionylation. Ceramides inhibit protein kinase Cβ, which phosphorylates and activates p300/CBP for histone H3 Lys-18 acetylation. In addition, p300 degradation by the ubiquitin-proteasome complex causes a decrease in the expression and activity of p300 and consequent histone H3/H4 hypoacetylation. Meanwhile, essential proteins in the DNA replication fork, chromatin remodeling complex, and RNA polymerase II mediators are down-regulated in differentiated cells, regulating DNA replication, DNA methylation, histone de novo acetylation, and H2B ubiquitination.