Transcription factor (TF) binding to DNA is fundamental for gene regulation. However, it remains unknown how the dynamics of TF–DNA interactions change during cell fate determination in vivo. We established imaging techniques to quantify TF–DNA binding in single cells of developing mouse embryos. We show how POU5F1 (OCT4) and SOX2 re-partition between specific and non-specific DNA sites as cells decide their fate in vivo. Furthermore, we discover heterogeneities in SOX2-DNA binding appearing as early as the 4-cell stage of development, and regulated by histone methylation, which predict cell fate. Finally, we develop new techniques to show how cells change their shape and position in the embryo to form the pluripotent inner mass.
References: White et al (2016) Cell; Samarage et al (2015) Dev. Cell; Fierro-Gonzalez et al (2013) Nat. Cell Bio.; Kaur et al (2013) Nat. Comm..