The enhancer landscape of pluripotent stem cells undergoes extensive 
reorganization during early mammalian development. The functions and mechanisms 
behind such reorganization, however, are unclear. Here, we show that the 
transcription factor GRHL2 is necessary and sufficient to activate an epithelial 
subset of enhancers as naive embryonic stem cells (ESCs) transition into 
formative epiblast-like cells (EpiLCs). Surprisingly, many GRHL2 target genes do 
not change in expression during the ESC-EpiLC transition. Instead, enhancers 
regulating these genes in ESCs diminish in activity in EpiLCs while 
GRHL2-dependent alternative enhancers become activated to maintain 
transcription. GRHL2 therefore assumes control over a subset of the naive 
network via enhancer switching to maintain expression of epithelial genes upon 
exit from naive pluripotency. These data evoke a model where the naive 
pluripotency network becomes partitioned into smaller, independent networks 
regulated by EpiLC-specific transcription factors, thereby priming cells for 
lineage specification.