EMBO J (2013) 32: 938–953 doi:; DOI: 10.1038/emboj.2013.31; published online March 08 2013
The transcription factor Oct4 plays a crucial role in the maintenance of the embryonic pluripotent state, but can also regulate early lineage commitment. In this issue of The EMBO Journal, Aksoy et al (2013) lend critical mechanistic insights into the ability of Oct4 to regulate and specify the primitive endodermal lineage. These regulatory actions are governed by alternative direct partnering of Oct4 with Sox17, instead of Sox2, that leads to global reprogramming of enhancer occupancy by Oct4 during primitive endoderm differentiation.