Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells.
EMBO Rep 2015 Sep; 16(9):1177-91.
Embryonic stem cell (ESC) identity is orchestrated by co-operativity between the transcription factors (TFs) Sox2 and the class V POU-TF Oct4 at composite Sox/Oct motifs. Neural stem cells (NSCs) lack Oct4 but express Sox2 and class III POU-TFs Oct6, Brn1 and Brn2. This raises the question of how Sox2 interacts with POU-TFs to transcriptionally specify ESCs versus NSCs. Here, we show that Oct4 alone binds the Sox/Oct motif and the octamer-containing palindromic MORE equally well. Sox2 binding selectively increases the affinity of Oct4 for the Sox/Oct motif. In contrast, Oct6 binds preferentially to MORE and is unaffected by Sox2. ChIP-Seq in NSCs shows the MORE to be the most enriched motif for class III POU-TFs, including MORE subtypes, and that the Sox/Oct motif is not enriched. These results suggest that in NSCs, co-operativity between Sox2 and class III POU-TFs may not occur and that POU-TF-driven transcription uses predominantly the MORE cis architecture. Thus, distinct interactions between Sox2 and POU-TF subclasses distinguish pluripotent ESCs from multipotent NSCs, providing molecular insight into how Oct4 alone can convert NSCs to pluripotency. EMBO Rep 2015 Sep; 16(9):1177-91.
Mistri, Tapan Kumar; Devasia, Arun George; Chu, Lee Thean; Ng, Wei Ping; Halbritter, Florian; Colby, Douglas; Martynoga, Ben; Tomlinson, Simon R; Chambers, Ian; Robson, Paul; and Wohland, Thorsten, "Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells." (2015). Faculty Research 2015. 150.