PXD056859

PXD056859 is an original dataset announced via ProteomeXchange.

Title	An Nlrp5-null mutation leads to attenuated de novo methylation in oocytes, accompanied by significant reduction in DNMT3L
Description	Nlrp5 encodes a core component of the subcortical maternal complex (SCMC) a cytoplasmic protein structure unique to the mammalian oocyte and cleavage-stage embryo. NLRP5 mutations have been identified in patients presenting with early embryo arrest, recurrent molar pregnancies and imprinting disorders. It was previously shown that oocytes with mutations in the human SCMC gene KHDC3L had globally impaired methylation, suggesting a requirement for integrity of the SCMC in the establishment of DNA methylation. Here, we present a multi-omic analysis of an Nlrp5-null mouse model. We detect global misregulation of maternal proteins, including profound reduction in the essential de novo methylation factor DNMT3L, which could contribute to attenuated de novo methylation we observe. In contrast, the maintenance methyltransferase DNMT1 exhibits normal cytoplasmic localisation. This provides evidence for mechanisms leading to downstream misregulation of imprinted genes, which in turn, may result in imprinting syndromes, multi-locus imprinting disturbances (MLID) and hydatidiform moles.
HostingRepository	PRIDE
AnnounceDate	2025-12-22
AnnouncementXML	Submission_2025-12-21_16:18:18.297.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Oxley
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-16 08:53:58	ID requested
⏵ 1	2025-12-21 16:18:19	announced

Nic Aodha L, Pokhilko A, Rosen LU, Galatidou S, Walewska E, Belton C, Galvao A, Okkenhaug H, Yu L, Nakhuda A, Mansfield B, Khan S, Oxley D, Barrag, á, n M, Kelsey G, An Nlrp5-null mutation leads to attenuated de novo methylation in oocytes, accompanied by a significant reduction in DNMT3L. Mol Hum Reprod, 31(4):(2025) [pubmed]

10.1093/molehr/gaaf055;

submitter keyword: Nlrp5, subcortical maternal complex, oocyte, DNA methylation

david oxley
contact affiliation	Babraham Institute, Cambridge, UK
contact email	david.oxley@babraham.ac.uk
lab head
David Oxley
contact affiliation	Babraham Institute
contact email	david.oxley@babraham.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/2025/12/PXD056859

PRIDE project URI

• PRIDE
  1. PXD056859
     1. Label: PRIDE project
     2. Name: An Nlrp5-null mutation leads to attenuated de novo methylation in oocytes, accompanied by significant reduction in DNMT3L