PXD080456-1

PXD080456 is an original dataset announced via ProteomeXchange.

Title	Reciprocal, methylation-dependent binding of Zfp57 and Gzf1 safeguards Dlk1-Dio3 imprinting during developmental reprogramming
Description	Genomic imprinting secures parent-specific gene expression through differential DNA methylation at imprinted control regions (ICRs). However, how unmethylated alleles resist de novo methylation remains unclear. Using an allelic Dlk1-Dio3 ICR methylation reporter and genome-wide loss-of-function screening, we identify the zinc finger protein GZF1 that binds the unmethylated maternal ICR and protects it from de novo methylation via a regulatory element containing GZF1 and ZFP57 motifs that mediates mutually exclusive, methylation-dependent binding. Loss of either factor causes reciprocal imprinting failure: Gzf1 loss induces maternal allele methylation, H3K4me3 depletion, and silencing of maternal transcripts, whereas Zfp57 loss results in maternalization. Remarkably, GZF1 protects the unmethylated ICR from de novo methylation in both oocytes and embryos, and its loss leads to perinatal death consistent with paternalization of the maternal allele. Together, our findings establish a reciprocal mechanism that maintains parental epigenetic asymmetry across both imprint establishment and embryonic reprogramming.
HostingRepository	PRIDE
AnnounceDate	2026-08-04
AnnouncementXML	Submission_2026-08-04_01:58:19.654.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liron Hoffman
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-01 17:42:09	ID requested
⏵ 1	2026-08-04 01:58:20	announced

Dataset with its publication pending

submitter keyword: methylation,mus musculus, gzf1, imprinting

Yonatan Stelzer
contact affiliation	Weizmann Institute of Science
contact email	yonatan.stelzer@weizmann.ac.il
lab head
Liron Hoffman
contact affiliation	Weizmann Institute of Science
contact email	liron.hoffman@weizmann.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD080456
     1. Label: PRIDE project
     2. Name: Reciprocal, methylation-dependent binding of Zfp57 and Gzf1 safeguards Dlk1-Dio3 imprinting during developmental reprogramming