A convenient research strategy for functional verification of epigenetic regulators during spermatogenesis.

Shan Li, Ying Yuan, Ke-Yu Zhang, Yi-Dan Guo, Lu-Tong Wang, Xiao-Yuan Zhang, Shu Zhang, Qi Yan, Rong Zhang, Jie Chen, Feng-Tang Yang, Jing-Rui Li
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Abstract

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.

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精子发生过程中表观遗传调节因子功能验证的便捷研究策略。
精子发生是一个基本过程,需要精原干细胞(SSC)中的表观遗传事件严格控制。从精原干细胞到精子的转变机制在很大程度上是未知的。大多数研究利用基因敲除小鼠来解释这一机制。然而,基因工程小鼠的生产成本高且耗时。在本研究中,我们提出了一种利用 RNA 干扰(RNAi)和睾丸移植方法的便捷研究策略。组蛋白H3赖氨酸9(H3K9)甲基化在精子发生过程中受到动态调控。由于含Jumonji结构域蛋白1A(JMJD1A)和含Jumonji结构域蛋白2C(JMJD2C)去甲基化酶催化组蛋白H3赖氨酸9二甲基化(H3K9me2),我们首先分析了这两种去甲基化酶的表达谱,然后研究了它们的功能。通过这种便捷的研究策略,我们发现正常的精子发生会因两种去甲基化酶的表达下调而受到破坏。这些结果表明,相对于基因敲除小鼠策略,这种策略可能是分析精子发生的一种简单的替代方法。
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