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. 2022 Apr;54(4):469-480.
doi: 10.1038/s41588-022-01040-z. Epub 2022 Apr 11.

DNMT3A-dependent DNA methylation is required for spermatogonial stem cells to commit to spermatogenesis

Mathilde Dura  1 , Aurélie Teissandier  1 , Mélanie Armand  1 , Joan Barau  2 , Clémentine Lapoujade  3 , Pierre Fouchet  3 , Lorraine Bonneville  1 , Mathieu Schulz  1 , Michael Weber  4 , Laura G Baudrin  5 , Sonia Lameiras  5 , Deborah Bourc'his  6
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DNMT3A-dependent DNA methylation is required for spermatogonial stem cells to commit to spermatogenesis

Mathilde Dura et al. Nat Genet. 2022 Apr.

Abstract

DNA methylation plays a critical role in spermatogenesis, as evidenced by the male sterility of DNA methyltransferase (DNMT) mutant mice. Here, we report a division of labor in the establishment of the methylation landscape of male germ cells and its functions in spermatogenesis. Although DNMT3C is essential for preventing retrotransposons from interfering with meiosis, DNMT3A broadly methylates the genome (with the exception of DNMT3C-dependent retrotransposons) and controls spermatogonial stem cell (SSC) plasticity. By reconstructing developmental trajectories through single-cell RNA sequencing and profiling chromatin states, we found that Dnmt3A mutant SSCs can only self-renew and no longer differentiate in association with spurious enhancer activation that enforces an irreversible stem cell gene program. Our findings therefore highlight a key function of DNA methylation in male fertility: the epigenetic programming of SSC commitment to differentiation and lifelong spermatogenesis supply.

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References

    1. Greenberg, M. V. C. & Bourc’his, D. The diverse roles of DNA methylation in mammalian development and disease. Nat. Rev. Mol. Cell Biol. 20, 590–607 (2019). - PubMed - DOI
    1. Weber, M. et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat. Genet. 39, 457–466 (2007). - PubMed - DOI
    1. Stadler, M. B. et al. DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 480, 490–495 (2011). - PubMed - DOI
    1. Xie, W. et al. Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell 153, 1134–1148 (2013). - PubMed - PMC - DOI
    1. Gifford, C. A. et al. Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell 153, 1149–1163 (2013). - PubMed - PMC - DOI

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