Figure 2. Features of OSKM in ESCs and during reprogramming.

(A) In ESCs, Oct4, Sox2, and Klf4 bind their own and each others promoters and enhancers, as well as those of many additional ESC-specific (pluripotency) genes. Further contributing to the pluripotency circuitry, many of these ESC-specific genes are also bound by various additional pluripotency regulators including Nanog and Esrrb, such that ESC-specific enhancers represent hotspots of pluripotency transcription factor binding. (B) (i) In ESCs (and many other cell types), cMyc targets most actively transcribed genes at the core promoter by binding high-affinity E-box sequences and functions by enhancing transcriptional elongation. Expression levels correlate with cMyc occupancy. (ii) Upon overexpression, cMyc does not appear to regulate new target genes, but amplifies the existing gene expression pattern by binding the same genes but now at elevated levels and occupying additional, low affinity E-box-like sequences in both the core promoter and enhancer regions of these genes. (C) Scheme illustrating different contributions of the reprogramming factors to the late phase of reprogramming, highlighting separable engagement of OSK and cMyc during reprogramming. Many genes occupied by cMyc in ESCs/iPSCs are already bound by this transcription factor and expressed in partially reprogrammed cells, which represent a late reprogramming intermediate. By contrast, OSK bind the promoter regions of many of their ESC-specific target genes only late in reprogramming, accompanying their transcriptional upregulation. This is particularly obvious for those genes that are co-bound by OSK in their promoter region in ESCs. (D) Chromatin can affect the ability of transcription factors to bind to their DNA motifs, which is thought to explain why most transcription factors bind to only a small subset of their recognition motifs in the genome. Here, we summarize the chromatin preferences of the four reprogramming factors early in reprogramming.