The enhancer landscape is dramatically restructured as nave 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 nave state requires Oct4 deacetylation by the NAD-dependent deacetylase, SirT1. The activity of SirT1 is reduced during the nave to primed transition, thereby increasing the acetylation of Oct4 and promoting its binding 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 provide strategies to manipulate epiblast cell state. SOURCE: Eric WilliamsLeonard Guarente Massachusetts Institute of Technology

Pluto Bioinformatics

GSE81494: Sirtuin 1 Promotes Nave Pluripotency by Deacetylation of Oct4 (RNA-seq)