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FoxO transcription factors actuate the formative pluripotency specific gene expression programme [ATAC-Seq]

GSE253472 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2024/07/25 Platform GPL24247
Summary
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.
Published in
FoxO transcription factors actuate the formative pluripotency specific gene expression programme
Santini L, Kowald S, Cerron-Alvan LM et al. · Nature communications 2024 · PMID 39251582 · doi:10.1038/s41467-024-51794-9
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Direct links to NCBI, no account and no request form: the whole study as GSE253472_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1065871 and SRA study SRP484261. Searching any of these in the dataset finder brings you back here.

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