Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition.

ABSTRACT: The POU family transcription factor Oct4 plays pivotal roles in regulating pluripotency and somatic cell reprogramming. Previous studies have indicated an important role for major groove contacts in Oct4-DNA recognition; however, the contributions of the RK motif in the POUh domain and the linker segment joining the two DNA-binding domains remain poorly understood. Here, by combining molecular modelling and functional assays, we find that the RK motif is essential for Oct4-DNA association by recognizing the narrowed DNA minor groove. Intriguingly, computational simulations reveal that the function of the RK motif may be finely tuned by H-bond interactions with the partially disordered linker segment and that breaking these interactions significantly enhances the DNA binding and reprogrammi

SUBMITTER: Kong X 

PROVIDER: S-EPMC4482079 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature