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PXD009200 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleGlobal hyperactivation of enhancers stabilizes human and mouse naïve pluripotency
DescriptionThe transition of pluripotent stem cells (PSCs) from primed to naïve states constitutes a prototypical example of cellular plasticity. The naïve state can be stabilized by defined chemical cocktails that block extracellular signals, notably including the MEK pathway. However, little is known regarding the underlying transcriptional mechanisms. Here, we report that the transcriptional landscape of the naïve state can be mimicked in mouse and human PSCs by stimulating transcriptional enhancers. This is attained by inhibiting the CDK8 and CDK19 kinases, which are negative regulators of Mediator, a critical component of enhancer function. Mechanistically, CDK8/19i triggers a global increase in the recruitment of RNA Pol II at promoters and enhancers, hyperactivating enhancers and their target genes. Lastly, the emergence of naïve pluripotency in the pre-implantation epiblast coincides with a marked reduction in CDK8/19 activity, and CDK8/19i blocks its subsequent developmental progression. These findings suggest that naïve pluripotency during development includes hyperactivation of enhancers and can be captured in vitro, either by blunting extracellular signaling, or by stimulating enhancer-driven transcription. These principles may apply to other cellular transitions.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAna Martinez
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-03-13 08:18:36ID requested
12020-09-29 03:36:45announced
Publication List
Dataset with its publication pending
Keyword List
curator keyword: Biological
submitter keyword: Stem cells, phosphorylation, pluripotency
Contact List
Javier Muñoz Peralta
contact affiliationProteomics Unit, Spanish Cancer Research Centre, Madrid, Spain
contact emailjmunozpe@cnio.es
lab head
Ana Martinez
contact affiliationSpanish National Cancer Research Centre
contact emailamdelval@cnio.es
dataset submitter
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Dataset FTP location
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