Accession PRJNA1065872
Title FoxO transcription factors actuate the formative pluripotency specific gene expression programme [ChIP-Seq]
Relevance ModelOrganism
Data types Epigenomics
Sample scope Multiisolate
Organism Mus musculus [Taxonomy ID: 10090]
Description Naïve pluripotency is sustained by a self-reinforcing gene regulatory network (GRN) comprising core and naïve pluripotency-specific transcription factors (TFs). Upon exiting naïve pluripotency, ES cells transition through a formative post-implantation-like pluripotent state. However, the mechanisms underlying disengagement from the naïve GRN and initiation of the formative GRN remain unclear. Here, we demonstrate that phosphorylated AKT acts as a gatekeeper that prevents nuclear localization of FoxO TFs in naïve ESCs. PTEN-mediated reduction of AKT activity allows nuclear entry by FoxO TFs, enforcing a cell fate transition by binding and activating formative pluripotency-specific enhancers. Indeed, FoxO TFs are necessary and sufficient for transition from the naïve to the formative pluripotent state. Our work uncovers a pivotal role for FoxO TFs and AKT signalling in mechanisms underlying the exit from naïve pluripotency, a critical early embryonic cell fate transition. Overall design: Chromatine-immunoprecipitation DNA sequencing (ChIP-seq) for FoxO1 and FoxO3 in WT and Pten KO mESC, in pluripotency supporting conditions (2i) and 24hours after 2i withdrawal (N24).
External link
Link description
Organization Max Perutz Labs, University of Vienna
Data Source NCBI

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Experiment (32)  show -