当前位置:科学网首页 > 小柯机器人 >详情
DNMT3A依赖性DNA甲基化调控精子发育
作者:小柯机器人 发布时间:2022/4/15 16:15:10

法国巴黎文理研究大学Deborah Bourc’his团队发现,DNA甲基转移酶(DNMT)3A依赖性DNA甲基化是精原干细胞发育为精子所必需的。相关论文于2022年4月11日发表在《自然-遗传学》杂志上。

研究人员揭示了雄性生殖细胞甲基化图谱及其在精子发生中的功能分工。尽管DNMT3C对于防止反转录转座子干扰减数分裂至关重要,但DNMT3A介导广泛的基因组甲基化(DNMT3C依赖性反转录转座子除外)并调控精原干细胞(SSC)的可塑性。通过单细胞RNA测序和染色质状态分析重建发育轨迹,研究发现Dnmt3A突变的SSC只能自我更新,不再与伪增强子激活相关分化,而伪增强子激活会促进一种不可逆的干细胞基因程序。

总之,该研究结果揭示了DNA甲基化在男性生育过程中的关键功能:SSC的表观遗传基序调控了精子分化和终生供应。

据悉,DNA甲基化在精子发生中起关键作用, DNMT突变雄性小鼠不育印证了这一点。

附:英文原文

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

Author: Dura, Mathilde, Teissandier, Aurlie, Armand, Mlanie, Barau, Joan, Lapoujade, Clmentine, Fouchet, Pierre, Bonneville, Lorraine, Schulz, Mathieu, Weber, Michael, Baudrin, Laura G., Lameiras, Sonia, Bourchis, Deborah

Issue&Volume: 2022-04-11

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. 

DOI: 10.1038/s41588-022-01040-z

Source: https://www.nature.com/articles/s41588-022-01040-z

 

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex