PXD032184-1

PXD032184 is an original dataset announced via ProteomeXchange.

Title	Pramel7-Cul2 axis establishes ground-state gene expression in embryonic stem cells
Description	Pluripotency is established in E4.5 preimplantation epiblast, the founder populations of the adult embryo. The establishment of in vitro models that closely resemble ground-state pluripotency represents an important opportunity to study early embryo development. Pramel7, a protein highly expressed in the inner cell mass (ICM) but expressed at low levels in embryonic stem cells (ESCs), was implicated in the establishment of ground-state pluripotency. Increasing Pramel7 expression in developmentally advanced ESC+serum causes global DNA hypomethylation and induces a gene expression signature close to developmental ground-state. However, how Pramel7 affects gene expression remains elusive. Here we show that Pramel7 associates and recruits to chromatin Cullin2 (Cul2), a component of Cullin2-RING E3 ubiquitin ligase complex that is implicated in proteasomal degradation of target substrates. Pramel7-Cul2 interaction is required for the establishment of ground-state gene expression signature. We show that Pramel7/Cul2 directly target many components of repressive chromatin, including components of the Nucleosome Remodelling and Deacetylase (NuRD) complex, for degradation. We identified a set of Pramel7-regulated genes that depend on Cul2 and associate with the NuRD component Chd4. The majority of these genes are upregulated in ESCs expressing Pramel7 and linked to pluripotency pathways. Finally, we show that Chd4 binding to these genes is impaired by Pramel7 in a Cul2-dependent manner. Our data link proteasome pathway to the establishment of ground-state gene expression, offering insights that could facilitate the establishment of in vitro models to reproduce the in vivo ground-state pluripotency.
HostingRepository	PRIDE
AnnounceDate	2024-01-08
AnnouncementXML	Submission_2024-01-08_05:45:47.654.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Deena Leslie Pedrioli
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-10 11:58:02	ID requested
⏵ 1	2024-01-08 05:45:48	announced

Dataset with its publication pending

submitter keyword: pluripotency, embryonic stem cells,Pramel7, proteasome, Cullin 2

Raffaella Santoro
contact affiliation	Department of Molecular Mechanisms of Disease, DMMD University of Zurich 8057 Zurich Switzerland
contact email	raffaella.santoro@dmmd.uzh.ch
lab head
Deena Leslie Pedrioli
contact affiliation	University of Zürich
contact email	deena.lesliepedrioli@dmmd.uzh.ch
dataset submitter

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/2024/01/PXD032184

PRIDE project URI

• PRIDE
  1. PXD032184
     1. Label: PRIDE project
     2. Name: Pramel7-Cul2 axis establishes ground-state gene expression in embryonic stem cells