Evidence map›Paper›PMID 41574437›Full record

ArticleNucleic acids research2026

A novel dual histone mark reader ZCWPW2 regulates meiotic recombination through lactylation and transcriptional regulation in humans and mice.

Tiechao Ruan, Jun Ma, Gan Shen, Xiang Wang, Yihong Yang, Liangchai Zhuo, Chuan Jiang, Guicheng Zhao, Yunchuan Tian, Shikun Zhao and 11 more

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In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

21 authors.

Tiechao RuanDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Jun MaDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Gan ShenDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Xiang WangDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Yihong YangDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Liangchai ZhuoDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Chuan JiangDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Guicheng ZhaoHuman Sperm Bank, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Yunchuan TianDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Shikun ZhaoDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Ruixi ZhouDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.ORCID 0000-0002-4409-1595
Mohan LiuDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Xinyao TangDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Yingteng ZhangDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Chanjuan ZhaoWest China Institutes of Women and Children's Health, West China Second University Hospital, Sichuan University. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education. Si Chuan, Chengdu 610041, China.
Jincheng ZhangDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Dingming LiDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Xiaohui JiangHuman Sperm Bank, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Dezhi MuDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Lingbo WangShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, State Key Laboratory of Genetics and Development of Complex Phenotypes, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200433, China.ORCID 0000-0002-0962-8457
Ying ShenDepartment of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.ORCID 0000-0002-6346-1002

Funding

National Key R&D Program of China 2021YFC2701700National Key R&D Program of China 2021YFC2701704National Natural Science Foundation of China 32322017National Natural Science Foundation of China 32470909National Natural Science Foundation of China 82271749National Natural Science Foundation of China 82471650Sichuan Science and Technology Program 2024YFFK0267
6 · The paper itself

Abstract

Meiotic recombination ensures accurate chromosome segregation and genetic diversity during gametogenesis, and its disruption leads to infertility. The dual histone methylation writer-reader system, in which PRDM9 deposits H3K4me3 and H3K36me3 marks at nucleosomes to define recombination hotspots and ZCWPW1 acts as a reader recognizing these marks, is essential for meiotic recombination. However, the regulatory mechanisms of this system remain unclear. Here, we showed that deficiency of ZCWPW2 causes recombination defects in humans and mice, including impaired homologous chromosome synapsis and defective DNA double-strand break repair. CUT&Tag analysis revealed that ZCWPW2 exhibits increased enrichment at dual H3K4me3 and H3K36me3 sites in the presence of PRDM9, while binding to promoter regions independently of PRDM9 to regulate meiotic transcription. Mass spectrometry further showed that ZCWPW2 forms a complex with ZCWPW1 and interacts with recombination-associated proteins in a ZCWPW1-dependent manner. Mechanistically, we demonstrate that the ZCWPW1-ZCWPW2 complex enhances the functions of key lactylation regulators LDHA and EP300, thereby promoting lactylation of recombination-associated proteins and stabilizing their abundance. Collectively, we identify ZCWPW2 as a previously unrecognized but essential factor in meiotic recombination, elucidate the molecular mechanism of the PRDM9/ZCWPW1/ZCWPW2 system in regulating recombination, and uncover a critical role for lactylation in meiosis.

Indexed as

HistonesHomologous RecombinationMeiosisAnimalsCell Cycle ProteinsChromosome PairingDNA Breaks, Double-StrandedGene Expression RegulationHistone-Lysine N-MethyltransferaseHumansMaleMicePromoter Regions, GeneticRecombination, GeneticTranscription, GeneticCell Cycle ProteinsHistone-Lysine N-MethyltransferaseHistonesPRDM9 protein, humanprdm9 protein, mouseZcwpw1 protein, mouse

Identifiers

PMID41574437
PMCPMC12828234

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.