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PXD070427

PXD070427 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA novel dual histone mark reader ZCWPW2 regulates meiotic recombination through lactylation and transcriptional control in humans and mice
DescriptionMeiotic recombination ensures proper chromosome segregation and genetic diversity during gametogenesis, and its disruption leads to infertility. It is known that the dual histone methylation writer–reader system, in which PRDM9 deposits H3K4me3 and H3K36me3 marks at nucleosomes to specify recombination hotspots and ZCWPW1 functions as a reader recognizing these marks, is essential for meiotic recombination. However, the regulatory mechanism of this system remains unclear. Here, Deficiency of ZCWPW2 causes recombination defects, with impairment in homologous synapsis and DNA double-strand break repair. CUT&Tag and mass spectrometry analyses revealed that ZCWPW2 recognizes PRDM9-mediated dual histone methylation and interacts with ZCWPW1 to form a complex that recruits recombination-associated proteins to hotspots. Additionally, ZCWPW2 independently binds to promoter regions to regulate meiotic transcription. Lactylome and proteome analyses demonstrated that the ZCWPW1–ZCWPW2 complex interacts with and maintains the activity of lactate dehydrogenase LDHA, and together with ZCWPW2-driven transcription of lactylation writer EP300, to promote lactylation of recombination-associated proteins and stabilize their expression at hotspots. Collectively, we identified ZCWPW2 as a previously unrecognized yet indispensable factor supporting the function of PRDM9/ZCWPW1 during meiotic recombination, elucidated the molecular mechanism of the PRDM9/ZCWPW1/ZCWPW2 system in regulating recombination, and uncovered a critical role for lactylation in meiosis.
HostingRepositoryPRIDE
AnnounceDate2026-01-07
AnnouncementXMLSubmission_2026-01-07_03:15:51.530.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYing Shen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-11-06 16:50:55ID requested
12026-01-07 03:15:52announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Meiotic recombination
ZCWPW1–ZCWPW2 complex
PRDM9/ZCWPW1/ZCWPW2 system
LDHA
EP300
lactylation
Contact List
Ying Shen
contact affiliationWest China Second University Hospital, Sichuan University
contact emailyingcaishen01@163.com
lab head
Ying Shen
contact affiliationWest China Second University Hospital, Sichuan University
contact emailyingcaishen01@163.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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