PXD047331

PXD047331 is an original dataset announced via ProteomeXchange.

Title	C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline
Description	In the male mouse germline, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon methylation and whether this pathway functions to protect the human germline remains unknown. We identified loss-of-function variants in human SPOCD1 that cause defective transposon silencing and male infertility. Through the analysis of one of these pathogenic alleles, we discovered that the uncharacterised protein C19ORF84 interacts with SPOCD1. DNMT3C, the DNA methyltransferase responsible for transposon methylation, associates with SPOCD1 and C19ORF84 in foetal gonocytes. Furthermore, C19ORF84 is essential for piRNA-directed DNA methylation and male mouse fertility. Finally, C19ORF84 mediates the in vivo association of SPOCD1 with the de novo methylation machinery. In summary, we have discovered a conserved role for the human piRNA pathway in transposon silencing and C19ORF84, an uncharacterised protein essential for orchestrating piRNA-directed DNA methylation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:29:24.204.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ansgar Zoch
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-28 06:38:41	ID requested
1	2024-02-14 05:30:06	announced
⏵ 2	2024-10-22 06:29:24	announced	2024-10-22: Updated project metadata.

10.1016/J.MOLCEL.2024.01.014;

submitter keyword: C19ORF84, Spocd1, piRNA, DNA methylation

Donal O'Carroll
contact affiliation	University of Edinburgh
contact email	donal.ocarroll@ed.ac.uk
lab head
Ansgar Zoch
contact affiliation	Institute for Stem Cell Research; Wellcome Centre for Cell Biology; University of Edinburgh
contact email	ansgar.zoch@ed.ac.uk
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/2024/02/PXD047331

PRIDE project URI

• PRIDE
  1. PXD047331
     1. Label: PRIDE project
     2. Name: C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline