PXD030666-1

PXD030666 is an original dataset announced via ProteomeXchange.

Title	Systematic identification of factors involved in the silencing of germline genes in mouse embryonic stem cells
Description	In mammals, many germline genes are repressed by epigenetic mechanisms to prevent their illegitimate expression in embryonic and somatic cells. To advance our understanding of the complete mechanisms restricting the expression of germline genes in mammals, we analyzed the chromatin signature of germline genes and performed a genome-wide CRISPR-Cas9 knock-out screen for genes involved in germline gene repression using a reporter system in which GFP is under the control of the epigenetically repressed Dazl germline promoter in mouse embryonic stem cells (ESCs). We showed that the repression of germline genes mainly depends on the polycomb complex PRC1.6 and DNA methylation, which function additively in mouse ESCs. Furthermore, we identified and validated several novel genes involved in the repression of germline genes, and characterized three of them: Usp7, Shfm1 (also known as Sem1) and Erh. Inactivation of Usp7, Shfm1 or Erh led to the upregulation of germline genes, as well as retrotransposons for Shfm1, in mouse ESCs. Functionally, Usp7 acts at two levels: firstly it associates with PRC1.6 components and represses germline genes independently of DNA methylation, and secondly it facilitates DNA methylation deposition at germline genes for long term repression. In summary, our study provides a global view of the epigenetic mechanisms and novel factors required for silencing germline genes in embryonic cells.
HostingRepository	PRIDE
AnnounceDate	2023-02-03
AnnouncementXML	Submission_2023-02-03_06:54:40.344.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JohanaChicher
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-30 03:36:46	ID requested
⏵ 1	2023-02-03 06:54:40	announced

Dataset with its publication pending

submitter keyword: Germline genes, Erh, PRC1.6, Shfm1, CRISPR-Cas9 screen, DNA methylation, ES cells, Usp7

MichaelWeber
contact affiliation	CNRS UMR7242, Biotechnology and Cell Signaling, 300 Bd Sébastien Brant, 67412 Illkirch Cedex, France University of Strasbourg
contact email	michael.weber@unistra.fr
lab head
JohanaChicher
contact affiliation	Université de Strasbourg, Plateforme Protéomique Strasbourg-Esplanade, Centre National de la Recherche Scientifique
contact email	j.chicher@ibmc-cnrs.unistra.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030666
     1. Label: PRIDE project
     2. Name: Systematic identification of factors involved in the silencing of germline genes in mouse embryonic stem cells