PRDM14 Drives OCT3/4 Recruitment via Active Demethylation in the Transition from Primed to Naive Pluripotency

Summary Primordial germ cells (PGCs) are specified from epiblast cells in mice. Genes associated with naive pluripotency are repressed in the transition from inner cell mass to epiblast cells, followed by upregulation after PGC specification. However, the molecular mechanisms underlying the reactivation of pluripotency genes are poorly characterized. Here, we exploited the in vitro differentiation of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to elucidate the molecular and epigenetic functions of PR domain-containing 14 (PRDM14). We found that Prdm14 overexpression in EpiLCs induced their conversion to ESC-like cells even in the absence of leukemia inhibitory factor in adherent culture. This was impaired by the loss of Kruppel-like factor 2 and ten-eleven translocation (TET) proteins. Furthermore, PRDM14 recruited OCT3/4 to the enhancer regions of naive pluripotency genes via TET-base excision repair-mediated demethylation. Our results provide evidence that PRDM14 establishes a transcriptional network for naive pluripotency via active DNA demethylation.
Graphical Abstract
Highlights • PRDM14 converts from EpiLCs to ESCs in adherent culture • EpiLC to ESC conversion by PRMD14 depends on KLF2 and TET-base excision repair pathway • PRDM14 enhances the recruitments of OCT3/4 at pluripotent genes
In this article, Seki and colleagues exploit an in vitro differentiation system of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to investigate the function of PRDM14. Overexpression of PRDM14 in EpiLCs induces the conversion from EpiLCs to ESCs through active DNA demethylation-mediated OCT3/4 recruitment at pluripotent genes in adherent culture.