PXD041214-1

PXD041214 is an original dataset announced via ProteomeXchange.

Title	Two-factor authentication underpins the precision of piRNA-directed LINE1 DNA methylation
Description	The PIWI-interacting RNA (piRNA) pathway guides the DNA methylation of young active transposons during male mouse germline development. piRNAs tether the PIWI protein MIWI2 (PIWIL4) to the nascent transposon transcript that results in DNA methylation through SPOCD1. Transposon methylation requires exacting precision: all copies need to be methylated yet, at the same time, off-target methylation must be avoided. However, the underlying mechanisms that ensure this precision remain unknown. Here, we show that SPOCD1 directly interacts with SPIN1, a chromatin reader that primarily binds H3K4me3 and this association is augmented by H3K9me3. The prevailing assumption is that all molecular events required for piRNA-directed DNA methylation occur after the engagement of MIWI2. Interestingly, we find that SPIN1 expression precedes that of both SPOCD1 and MIWI2. Furthermore, we demonstrate that young LINE1s, but not old copies are marked by H3K4me3 and H3K9me3 prior to the initiation of piRNA-directed DNA methylation. We generated a Spocd1 separation-of-function allele in the mouse that encodes a SPOCD1 variant that no longer interacts with SPIN1. We found that the SPOCD1-SPIN1 interaction is essential for spermatogenesis and piRNA-directed DNA methylation of young LINE1 elements. We propose that young LINE1 elements require a two-factor authentication process for DNA methylation, the first being the recruitment of SPIN1-SPOCD1 to licence the locus and the second is MIWI2 engagement with the nascent transcript, which is the trigger for methylation. In summary, independent events that licence, and trigger methylation underpin the basis of precision.
HostingRepository	PRIDE
AnnounceDate	2024-09-04
AnnouncementXML	Submission_2024-09-04_12:59:29.215.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	2023-03-30 06:30:32	ID requested
⏵ 1	2024-09-04 12:59:29	announced
2	2024-10-22 06:57:45	announced	2024-10-22: Updated project metadata.

10.1038/S41586-024-07963-3;

submitter keyword: transposon, piRNA, germline, DNA methylation,PIWI

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/2024/09/PXD041214

PRIDE project URI

• PRIDE
  1. PXD041214
     1. Label: PRIDE project
     2. Name: Two-factor authentication underpins the precision of piRNA-directed LINE1 DNA methylation