梅奥克-皮维尔1复合体调节rRNA转录以使精子干细胞分化
Toshihiro Kawasaki1,2, Toshiya Nishimura3, Naoki Tani4
1Department of Gene Function and Phenomics, National Institute of Genetics.
bioRxiv : the preprint server for biology
|November 28, 2024
概括
斑马鱼的干细胞保持低的rRNA转录. 梅奥克蛋白质防止Piwil1在核细胞中积累,促进rRNA合成和干细胞分化.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 分子遗传学 分子遗传学
背景情况:
- 核糖体生物生成对于干细胞的维护至关重要.
- 控制干细胞核糖体生物发生的调控机制在很大程度上是未知的.
- 精子干细胞 (SSC) 需要精确调节分化和增殖.
研究的目的:
- 研究Meioc在调节斑马鱼精子干细胞 (SSC) 特性中的作用.
- 阐明SSC差异化和rRNA转录控制背后的分子机制.
- 确定与Meioc相互作用的因素及其在胚芽颗粒中的功能.
主要方法:
- 对斑马鱼*meioc*突变体进行干细胞分化和rRNA表达的分析.
- 免疫光检测以确定Meioc和Piwil1.1的定位.
- 同免疫沉用于识别相互作用的蛋白质 (Piwil1,Setdb1,HP1α).
- 染色体免疫沉,然后进行定量PCR (ChIP-qPCR) 来评估45S-rDNA位点上的表观遗传修饰 (H3K9me3,CpG甲基化).
主要成果:
- *Meioc*突变体表现出受损的SSC分化和抑制的rRNA上调.
- 梅奥克枯竭导致Piwil1积聚在细胞核中,在那里它与45S前rRNA相互作用.
- 皮维尔1与表观遗传修饰剂Setdb1和HP1α相互作用.
- *Meioc*缺乏导致45S-rDNA区域的H3K9me3和CpG甲基化增加,这表明转录抑制.
- 减少Piwil1水平 (*piwil1*+/-) 在*meioc*-/-突变分子中部分恢复了SSC分化.
结论:
- 斑马鱼的SSC通过表观遗传抑制维持低rRNA转录,类似于*Drosophila*的piRNA目标.
- 梅奥克在防止Piwil1的核定位方面发挥着独特的作用,从而调节rRNA转录并促进SSC分化.
- 梅奥克-皮维尔1相互作用对控制核糖体生物发生和维持干细胞身份至关重要.
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