The enhancer landscape is dramatically restructured as naive preimplantation 
epiblasts transition to the post-implantation state of primed pluripotency. 
A key factor in this process is Otx2, which is upregulated during the early 
stages of this transition and ultimately recruits Oct4 to a different set of 
enhancers. In this study, we discover that the acetylation status of Oct4 
regulates the induction of the primed pluripotency gene network. Maintenance of 
the naive state requires the NAD-dependent deacetylase, SirT1, which 
deacetylates Oct4. The activity of SirT1 is reduced during the naive-to-primed 
transition; Oct4 becomes hyper-acetylated and binds to an Otx2 enhancer to 
induce Otx2 expression. Induction of Otx2 causes the reorganization of 
acetylated Oct4 and results in the induction of the primed pluripotency gene 
network. Regulation of Oct4 by SirT1 may link stem cell development to 
environmental conditions, and it may provide strategies to manipulate epiblast 
cell state.