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H3K9 Demethylases JMJD1A and JMJD1B Control Prospermatogonia to Spermatogonia Transition in Mouse Germline.
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-07-16 , DOI: 10.1016/j.stemcr.2020.06.013
Shunsuke Kuroki 1 , Ryo Maeda 1 , Masashi Yano 2 , Satsuki Kitano 3 , Hitoshi Miyachi 3 , Mikiko Fukuda 4 , Yoichi Shinkai 5 , Makoto Tachibana 6
Affiliation  

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.



中文翻译:

H3K9脱甲基酶JMJD1A和JMJD1B控制小鼠生殖细胞中精原细胞向精原细胞的转化。

组蛋白H3赖氨酸9(H3K9)甲基化由甲基转移酶和脱甲基酶动态调节。在精子发生中,生精子症在出生后分化为分化的或未分化的精子症。但是,从精原细胞向精原细胞过渡的表观遗传学调控尚不清楚。我们发现围产期前列腺癌的二甲基化H3K9(H3K9me2)含量极低,H3K9脱甲基酶JMJD1A和JMJD1B催化围产期前列腺癌中的H3K9me2去甲基化。胚胎种系中JMJD1A和JMJD1B的耗尽导致青春期后男性生殖细胞完全丧失,这表明H3K9me2脱甲基化对于维持男性种系至关重要。耗尽JMJD1A / JMJD1B的生殖细胞无法分化为功能性精原细胞。JMJD1同工酶通过在精原细胞向精原细胞的转变过程中通过H3K9脱甲基化作用,激活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。综上所述,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生精细胞分化为功能性生精细胞。

更新日期:2020-07-16
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