The transcription factors Nanog and Gata6 are critical to specify the epiblast 
versus primitive endoderm (PrE) lineages. However, little is known about the 
mechanisms that regulate the protein stability and activity of these factors in 
the developing embryo. Here we uncover an early developmental function for the 
Polycomb group member Bmi1 in supporting PrE lineage formation through Gata6 
protein stabilization. We show that Bmi1 is enriched in the extraembryonic 
(endoderm [XEN] and trophectodermal stem [TS]) compartment and repressed by 
Nanog in pluripotent embryonic stem (ES) cells. In vivo, Bmi1 overlaps with the 
nascent Gata6 and Nanog protein from the eight-cell stage onward before it 
preferentially cosegregates with Gata6 in PrE progenitors. Mechanistically, we 
demonstrate that Bmi1 interacts with Gata6 in a Ring finger-dependent manner to 
confer protection against Gata6 ubiquitination and proteasomal degradation. A 
direct role for Bmi1 in cell fate allocation is established by loss-of-function 
experiments in chimeric embryoid bodies. We thus propose a novel regulatory 
pathway by which Bmi1 action on Gata6 stability could alter the balance between 
Gata6 and Nanog protein levels to introduce a bias toward a PrE identity in a 
cell-autonomous manner.