PXD009200 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
Dataset with its publication pending |
Keyword List
curator keyword: Biological |
submitter keyword: pluripotency,Stem cells, phosphorylation |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/09/PXD009200 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD009200
- Label: PRIDE project
- Name: Global hyperactivation of enhancers stabilizes human and mouse naïve pluripotency