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

Autor: Dura M; Institut Curie, Paris Sciences et Lettres Research University, INSERM U934, CNRS UMR3215, Paris, France., Teissandier A; Institut Curie, Paris Sciences et Lettres Research University, INSERM U934, CNRS UMR3215, Paris, France., Armand M; Institut Curie, Paris Sciences et Lettres Research University, INSERM U934, CNRS UMR3215, Paris, France., Barau J; Institute of Molecular Biology, Mainz, Germany., Lapoujade C; Paris University and Paris-Saclay University, CEA, UMR SGCSR/E008, Fontenay-aux-Roses, France., Fouchet P; Paris University and Paris-Saclay University, CEA, UMR SGCSR/E008, Fontenay-aux-Roses, France., Bonneville L; Institut Curie, Paris Sciences et Lettres Research University, INSERM U934, CNRS UMR3215, Paris, France., Schulz M; Institut Curie, Paris Sciences et Lettres Research University, INSERM U934, CNRS UMR3215, Paris, France., Weber M; Biotechnology and Cell Signaling, University of Strasbourg, CNRS UMR7242, Illkirch Cedex, France., Baudrin LG; ICGex Next-Generation Sequencing Platform, Institut Curie, Paris Sciences et Lettres Research University, Paris, France., Lameiras S; ICGex Next-Generation Sequencing Platform, Institut Curie, Paris Sciences et Lettres Research University, Paris, France., Bourc'his D; Institut Curie, Paris Sciences et Lettres Research University, INSERM U934, CNRS UMR3215, Paris, France. deborah.bourchis@curie.fr.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2022 Apr; Vol. 54 (4), pp. 469-480. Date of Electronic Publication: 2022 Apr 11.
DOI: 10.1038/s41588-022-01040-z
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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