Dynamic changes in Sox2 spatio-temporal expression promote the second cell fate decision through

Tapan Kumar Mistri
Wibowo Arindrarto
Wei Ping Ng
Choayang Wang
Leng Hiong Lim
Lili Sun
Ian Chambers
Thorsten Wohland
Paul Robson, The Jackson Laboratory


Oct4 and Sox2 regulate the expression of target genes such as Nanog, Fgf4 and Utf1 , by binding to their respective regulatory motifs. Their functional cooperation is reflected in their ability to heterodimerise on adjacent cis regulatory motifs, the composite Sox/Oct motif. Given that Oct4 and Sox2 regulate many developmental genes, a quantitative analysis of their synergistic action on different Sox/Oct motifs would yield valuable insights into the mechanisms of early embryonic development. In this study, we measured binding affinities of Oct4 and Sox2 to different Sox/Oct motifs using fluorescence correlation spectroscopy (FCS). We found that the synergistic binding interaction is driven mainly by the level of Sox2 in the case of the Fgf4 Sox/Oct motif. Taking into account Sox2 expression levels fluctuate more than Oct4 , our finding provides an explanation on how Sox2 controls the segregation of the epiblast (EPI) and primitive endoderm (PE) populations within the inner cell mass (ICM) of the developing rodent blastocyst. Biochem J 2018 Feb 27 [Epub ahead of print]