H3K9 Demethylases JMJD1A and JMJD1B Control Prospermatogonia to Spermatogonia Transition in Mouse Germline
H3K9 Demethylases JMJD1A and JMJD1B Control Prospermatogonia to Spermatogonia Transition in Mouse Germline
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DOI：
10.1016/j.stemcr.2020.06.013
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发表时间：
2020-08-11
影响因子：
5.9
通讯作者：
Tachibana, Makoto
中科院分区：
文献类型：
--
作者：
Kuroki, Shunsuke;Maeda, Ryo;Tachibana, Makoto
组蛋白 H3 赖氨酸 9 (H3K9) 甲基化受甲基转移酶和去甲基化酶动态调节。在精子发生过程中，精原细胞在出生后分化为分化或未分化精原细胞。然而，原精原细胞向精原细胞转变的表观遗传调控在很大程度上是未知的。我们发现围产期精原细胞的二甲基化 H3K9 (H3K9me2) 水平极低，并且 H3K9 去甲基化酶 JMJD1A 和 JMJD1B 催化围产期精原细胞中的 H3K9me2 去甲基化。胚胎种系中 JMJD1A 和 JMJD1B 的缺失导致青春期后雄性生殖细胞完全丧失，表明 H3K9me2 去甲基化对于雄性种系维持至关重要。 JMJD1A/JMJD1B 耗尽的生殖细胞无法分化为功能性精原细胞。在精原细胞向精原细胞的转变过程中，JMJD1 同工酶通过 H3K9 去甲基化促进了几个精原干细胞维持基因的激活，我们认为这是精原细胞发育的关键。总之，JMJD1A/JMJD1B介导的H3K9me2去甲基化通过建立适当的基因表达谱来促进原精原细胞分化为功能性精原细胞。
Histone H3 lysine 9 (H3K9) methylation is dynamically regulated by methyltransferases and demethylases. In spermatogenesis, prospermatogonia differentiate into differentiating or undifferentiated spermatogonia after birth. However, the epigenetic regulation of prospermatogonia to spermatogonia transition is largely unknown. We found that perinatal prospermatogonia have extremely low levels of di-methylated H3K9 (H3K9me2) and that H3K9 demethylases, JMJD1A and JMJD1B, catalyze H3K9me2 demethylation in perinatal prospermatogonia. Depletion of JMJD1A and JMJD1B in the embryonic germline resulted in complete loss of male germ cells after puberty, indicating that H3K9me2 demethylation is essential for male germline maintenance. JMJD1A/JMJD1B-depleted germ cells were unable to differentiate into functional spermatogonia. JMJD1 isozymes contributed to activation of several spermatogonial stem cell maintenance genes through H3K9 demethylation during the prospermatogonia to spermatogonia transition, which we propose is key for spermatogonia development. In summary, JMJD1A/JMJD1B-mediated H3K9me2 demethylation promotes prospermatogonia to differentiate into functional spermatogonia by establishing proper gene expression profiles.