Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic 
stem (ES) cells, and their over-expression can induce pluripotency in both mouse 
and human somatic cells, indicating that these factors regulate the 
developmental signaling network necessary for ES cell pluripotency. However, 
systemic analysis of the signaling pathways regulated by Yamanaka factors has 
not yet been fully described. In this study, we identified the target promoters 
of endogenous Yamanaka factors on a whole genome scale using ChIP (chromatin 
immunoprecipitation)-on-chip in E14.1 mouse ES cells, and we found that these 
four factors co-occupied 58 promoters. Interestingly, when Oct4 and Sox2 were 
analyzed as core factors, Klf4 functioned to enhance the core factors for 
development regulation, whereas c-Myc seemed to play a distinct role in 
regulating metabolism. The pathway analysis revealed that Yamanaka factors 
collectively regulate a developmental signaling network composed of 16 
developmental signaling pathways, nine of which represent earlier unknown 
pathways in ES cells, including apoptosis and cell-cycle pathways. We further 
analyzed data from a recent study examining Yamanaka factors in mouse ES cells. 
Interestingly, this analysis also revealed 16 developmental signaling pathways, 
of which 14 pathways overlap with the ones revealed by this study, despite that 
the target genes and the signaling pathways regulated by each individual 
Yamanaka factor differ significantly between these two datasets. We suggest that 
Yamanaka factors critically regulate a developmental signaling network composed 
of approximately a dozen crucial developmental signaling pathways to maintain 
the pluripotency of ES cells and probably also to induce pluripotent stem cells.