阶段分离的CCER1协调了组织蛋白转变和男性生育能力的转变
Dongdong Qin1, Yayun Gu1,2, Yu Zhang3,4,5,6
1State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
Nature communications
|December 11, 2023
概括
卷状卷状富含谷氨酸蛋白1 (CCER1) 对于精子发育和男性生育能力至关重要. 它的缺乏会通过破坏精子染色质紧缩和表观遗传修饰而导致不孕.
科学领域:
- 生殖生物学 生殖生物学
- 分子遗传学 分子遗传学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 异形不孕症与遗传突变有关.
- 精子体的分化涉及复杂的遗传和表观遗传调节.
- 内在无序的蛋白质 (IDPs) 在细胞过程中起作用.
研究的目的:
- 为了研究卷状卷状富含谷氨酸蛋白1 (CCER1) 在男性生育能力中的作用.
- 了解CCER1在精子分和染色体凝聚中的分子机制.
- 为了确定CCER1变异与非阻塞性亚精子症 (NOA) 的关联.
主要方法:
- 关于CCER1缺陷的小鼠模型.
- 对基因转录的分析 (Tnp1/2,Prm1/2).
- 对基因组蛋白表观遗传修饰的评估.
- 关于CCER1自我组装和凝结物形成的体外研究.
- 在不育患者和对照人群中对人类CCER1变异的遗传分析.
主要成果:
- 在小鼠中,CCER1 缺乏导致缺陷的精子染色质紧缩和不孕.
- CCER1促进过渡蛋白和蛋白质胺转录,并在基因组-蛋白质胺转换期间调解基因组表观遗传修饰.
- CCER1形成了核液-液相分离的冷凝物.
- 在NOA患者中发现了人类CCER1 (hCCER1) 的功能丧失变体.
结论:
- 核CCER1的功能是作为男性生育能力所必不可少的相隔冷凝液.
- CCER1链接表观遗传修饰,基因组转变为原蛋白,以及染色质凝聚.
- 干扰CCER1凝聚物与男性不孕症有关.
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