Naive and primed pluripotency is characterized by distinct signaling 
requirements, transcriptomes, and developmental properties, but both cellular 
states share key transcriptional regulators: Oct4, Sox2, and Nanog. Here, we 
demonstrate that transition between these two pluripotent states is associated 
with widespread Oct4 relocalization, mirrored by global rearrangement of 
enhancer chromatin landscapes. Our genomic and biochemical analyses identified 
candidate mediators of primed state-specific Oct4 binding, including Otx2 and 
Zic2/3. Even when differentiation cues are blocked, premature Otx2 
overexpression is sufficient to exit the naive state, induce transcription of a 
substantial subset of primed pluripotency-associated genes, and redirect Oct4 to 
previously inaccessible enhancer sites. However, the ability of Otx2 to engage 
new enhancer regions is determined by its levels, cis-encoded properties of the 
sites, and the signaling environment. Our results illuminate regulatory 
mechanisms underlying pluripotency and suggest that the capacity of 
transcription factors such as Otx2 and Oct4 to pioneer new enhancer sites is 
highly context dependent.