ArticlePLoS genetics2013
A critical function of Mad2l2 in primordial germ cell development of mice.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- CTMP-REV7 axis modulates MHC-I antigen presentation via CDK1-AKT crosstalk in MSI-L/MSS colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Mechanisms of human germ cell development.Nature reviews. Molecular cell biology · 2026Review
- Primordial germ cell DNA demethylation and development require DNA translesion synthesis.Nature communications · 2024Article
- REV7: a small but mighty regulator of genome maintenance and cancer development.Frontiers in oncology · 2024Review
- Zfp296 knockout enhances chromatin accessibility and induces a unique state of pluripotency in embryonic stem cells.Communications biology · 2023Article
- REV7 in Cancer Biology and Management.Cancers · 2023Review
- Abnormal migration behavior linked to Rac1 signaling contributes to primordial germ cell exhaustion in Fanconi anemia pathway-deficient Fancg-/- embryos.Human molecular genetics · 2021Article
- DNA polymerase zeta contributes to heterochromatin replication to prevent genome instability.The EMBO journal · 2021Article
- REV7: Jack of many trades.Trends in cell biology · 2021Review
- Genome diversity and instability in human germ cells and preimplantation embryos.Seminars in cell & developmental biology · 2021Article
- The recent advances in non-homologous end-joining through the lens of lymphocyte development.DNA repair · 2020Review
- DNA polymerase ζ in DNA replication and repair.Nucleic acids research · 2019Review
- FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells.The EMBO journal · 2018Article
- MAD2L2 Promotes Open Chromatin in Embryonic Stem Cells and Derepresses the Dppa3 Locus.Stem cell reports · 2017Article
- Testis Transcriptome Modulation in Klinefelter Patients with Hypospermatogenesis.Scientific reports · 2017Article
- The Polymerase Activity of Mammalian DNA Pol ζ Is Specifically Required for Cell and Embryonic Viability.PLoS genetics · 2016Article
- The multifaceted roles of the HORMA domain in cellular signaling.The Journal of cell biology · 2015Review
- Kif18a is specifically required for mitotic progression during germ line development.Developmental biology · 2015Article
- REV7/MAD2L2: the multitasking maestro emerges as a barrier to recombination.The EMBO journal · 2015Article
- Destabilization of pluripotency in the absence of Mad2l2.Cell cycle (Georgetown, Tex.) · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of primordial germ cells (PGCs) involves several waves of epigenetic reprogramming. A major step is following specification and involves the transition from the stably suppressive histone modification H3K9me2 to the more flexible, still repressive H3K27me3, while PGCs are arrested in G2 phase of their cycle. The significance and underlying molecular mechanism of this transition were so far unknown. Here, we generated mutant mice for the Mad2l2 (Mad2B, Rev7) gene product, and found that they are infertile in both males and females. We demonstrated that Mad2l2 is essential for PGC, but not somatic development. PGCs were specified normally in Mad2l2(-/-) embryos, but became eliminated by apoptosis during the subsequent phase of epigenetic reprogramming. A majority of knockout PGCs failed to arrest in the G2 phase, and did not switch from a H3K9me2 to a H3K27me3 configuration. By the analysis of transfected fibroblasts we found that the interaction of Mad2l2 with the histone methyltransferases G9a and GLP lead to a downregulation of H3K9me2. The inhibitory binding of Mad2l2 to Cyclin dependent kinase 1 (Cdk1) could arrest the cell cycle in the G2 phase, and also allowed another histone methyltransferase, Ezh2, to upregulate H3K27me3. Together, these results demonstrate the potential of Mad2l2 in the regulation of both cell cycle and the epigenetic status. The function of Mad2l2 is essential in PGCs, and thus of high relevance for fertility.
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