In 5 of 6 foreground sets, POU motifs were more strongly associated with the transgenic state than with the tumor state. This difference was most pronounced in analyses of downregulated and PI-103 specific downregulated gene sets, where dots representing POU matrices are located far away from the mass of points. Notably, sites of some POU motifs were also more than 2- fold enriched in promoters of downregulated genes in tumor. Oct1 matrices were the top ranked motifs in downregulated and specific downregulated genes in tumor. However, promoters of upregulated genes were detectably enriched with POU sites in the transgenic state only. These results suggest that POU factors contributed to the switch from transgenic to tumor state. Furthermore, their activity may represent a major cause of observed downregulation events. Among the POU transcription factors represented by matrices identified in the analyses, the expression profile of Pou5f1 resembled well the observed progression-state specific enrichment of its binding sites. The Pou5f1 gene exhibited a high fold change in the transgenic state, which had decreased in the tumor state. Indeed, the Pou5f1 gene is specifically expressed in embryonic stem cells and in tumor cells, but not in cells of differentiated tissues. Transcription factors with a Forkhead domain also showed association with the transgenic state. This signal was best observed in upregulation and cell cycle gene sets, yet subtle enrichment in transgenic promoters could also be detected in specific downregulation and specific upregulation, where the FREAC2 motif ranked among the top 15 PWMs. In the upregulation set, Foxd3 binding sites showed the strongest signal after Oct1 sites. This would support a potential role of Oct4, as corepression through overlapping binding sites of Oct4 and Foxd3 was previously reported. According to expression measurements, Foxd3 was potentially downregulated in both progression states, although measured expression differences were not statistically significant. Instead, Foxc1 expression parallels the stronger enrichment of Forkhead binding sites in transgenic promoter sets, as it is specifically upregulated in the early progression state. Promoters of upregulated genes in tumor were associated with binding sites of cell cycle regulators such as AP1-like factors, STAT, and E2f, of which Atf3, Jun, and E2f3 were significantly upregulated in both transgenic and tumor cells. This finding supports the stronger regulation of cell cycle processes in tumor detected by comparative GO analysis. The analysis of cell cycle gene promoters suggests E2f factors as the most important regulators in both states, whereas a tendency towards higher q-values in the tumor set was observed for several E2f motifs. Notably, the Myc-associated zinc finger protein was detected in the transgenic cell cycle gene set.