An Extended Transcriptional Network for Pluripotency of Embryonic Stem Cells

Much attention has focused on a small set of transcription factors that maintain human or mouse embryonic stem (ES) cells in a pluripotent state. To gain a more complete understanding of the regulatory network that maintains this state, we identified target promoters of nine transcription factors, including somatic cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) and others (Nanog, Dax1, Rex1, Zpf281, and Nac1), on a global scale in mouse ES cells. We found that target genes fall into two classes: promoters bound by few factors tend to be inactive or repressed, whereas promoters bound by more than four factors are largely active in the pluripotent state and become repressed upon differentiation. Furthermore, we propose a transcriptional hierarchy for reprogramming factors and broadly distinguish targets of c-Myc versus other factors. Our data provide a resource for exploration of the complex network maintaining pluripotency.