Fig. 2.

Transcriptional activities and protein–protein interactions of stemness factors (modified from [158]). a Oct4 transcription factor can directly activate gene transcription by binding to octamer sites (first line). Activation may also occur via bridge proteins (second line). Moreover, Oct4 can repress transcription by either direct binding to promoters (third line) or neutralization of activators such as FoxD3 (fourth line). b POU and HMG transcription factors such as Oct4 and Sox2 confer their transcriptional activity often in concert on target genes. Two examples are drawn schematically demonstrating that Oct4 and Sox2 are able to form dissimilar structures of heterodimers that act differently on particular downstream genes. c Nanog is able to block differentiation signals induced by bone morphogenic protein and intracellularly mediated by Smad1 through heterodimerization with Smad1