PXD009200

PXD009200 is an original dataset announced via ProteomeXchange.

Title	Global hyperactivation of enhancers stabilizes human and mouse naïve pluripotency
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:12:57.281.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ana Martinez
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-13 08:18:36	ID requested
1	2020-09-29 03:36:45	announced
⏵ 2	2024-10-22 05:12:57	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: pluripotency,Stem cells, phosphorylation

Javier Muñoz Peralta
contact affiliation	Proteomics Unit, Spanish Cancer Research Centre, Madrid, Spain
contact email	jmunozpe@cnio.es
lab head
Ana Martinez
contact affiliation	Spanish National Cancer Research Centre
contact email	amdelval@cnio.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009200
     1. Label: PRIDE project
     2. Name: Global hyperactivation of enhancers stabilizes human and mouse naïve pluripotency