PXD060851

PXD060851 is an original dataset announced via ProteomeXchange.

Title	A nowhere-to-hide mechanism ensures complete piRNA-directed LINE1 methylation
Description	The mouse PIWI-interacting RNA (piRNA) pathway provides anti-transposon immunity to the developing male germline by directing transposon DNA methylation. The first step in this process is the recruitment of SPOCD1 to young LINE1 loci 1 followed in the second step by piRNA-mediated tethering of the PIWI protein MIWI2 (PIWIL4) to the nascent transposon transcript. To protect the germline, the piRNA pathway needs to methylate all active transposon copies but how this is achieved remains unknown. Here, we show that nuclear piRNA and de novo methylation factors are all euchromatic. We find that SPOCD1 directly interacts with the nuclear pore component TPR, which forms heterochromatin exclusion zones adjacent to nuclear pores. In foetal gonocytes undergoing piRNA-directed DNA methylation, TPR is found both at the nuclear periphery but also abundantly throughout the nucleoplasm. We found that the SPOCD1-TPR interaction is required for complete non-stochastic piRNA-directed LINE1 methylation. The loss of the SPOCD1-TPR interaction results in a fraction of SPOCD1 and other chromatin-bound piRNA factors to relocalise to constitutive heterochromatin where they are no longer accessible to MIWI2 and the de novo methylation machinery. We propose that TPR-mediated heterochromatin exclusion provides a nowhere-to-hide mechanism for SPOCD1-bound LINE1 loci throughout the nucleoplasm. In summary, the piRNA pathway has co-opted TPR to guarantee LINE1s are euchromatic and accessible to the piRNA and de novo methylation machineries.
HostingRepository	PRIDE
AnnounceDate	2025-11-11
AnnouncementXML	Submission_2025-11-11_02:21:59.298.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christos Spanos
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-16 10:13:26	ID requested
⏵ 1	2025-11-11 02:21:59	announced

Dataset with its publication pending

submitter keyword: PIWI proteins, piRNA, SPOCD1 and TPR,Germline, transposons

Donal O'Carroll
contact affiliation	University of edinburgh
contact email	donal.ocarroll@ed.ac.uk
lab head
Christos Spanos
contact affiliation	University of Edinburgh
contact email	spanos.christos@gmail.com
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/2025/11/PXD060851

PRIDE project URI

• PRIDE
  1. PXD060851
     1. Label: PRIDE project
     2. Name: A nowhere-to-hide mechanism ensures complete piRNA-directed LINE1 methylation