Fiche publication
Date publication
avril 2022
Journal
Nature genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr WEBER Mickaël
Tous les auteurs :
Dura M, Teissandier A, Armand M, Barau J, Lapoujade C, Fouchet P, Bonneville L, Schulz M, Weber M, Baudrin LG, Lameiras S, Bourc'his D
Lien Pubmed
Résumé
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.
Mots clés
Animals, DNA Methylation, genetics, DNA Modification Methylases, genetics, Male, Mice, Retroelements, Spermatogenesis, genetics, Spermatogonia, metabolism, Stem Cells
Référence
Nat Genet. 2022 Apr;54(4):469-480
