Figure 7. Role of the four factors during reprogramming.

(A) c-Myc is a major contributor to the down-regulation of fibroblast-specific genes at the beginning of the reprogramming process (i). In iPS cells, c-Myc binds and activates many ES-cell specific genes with roles in metabolic regulation, often with the other three factors (iii). For many of these target genes, binding and activation is also found in partially reprogrammed cells (ii). Target genes that are co-bound by Oct4, Sox2 and Klf4 in ES/iPS cells encode some of the most highly expressed regulators of pluripotency (v) and are not bound and activated at the partially reprogrammed state (iv). Our data suggest that the targeting of OSK to these genes represents a barrier to the reprogramming process and that c-Myc-bound genes largely become activated during earlier steps.

(B) State of histone H3K4 and K27 trimethylation within promoter regions of genes that become most highly activated during reprogramming and that are co-bound by Oct4, Sox2 and Klf4 in ES/iPS cells but not partially reprogrammed cells.