在胚胎发育过程中,Daxx的基因组辅导功能是不可或缺的
Chang Sun1,2, Yuan Qi3, Natalie Fowlkes4
1Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Cell death & disease
|August 26, 2023
概括
达克斯蛋白在小鼠发育过程中具有不同的作用. 破坏其与Atrx的相互作用会影响复原病毒,而破坏其H3.3的相互作用会影响产后生存和免疫细胞.
科学领域:
- 表观遗传学和基因调控
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 达克斯是胚胎发育必不可少的基因素陪伴剂.
- 达克斯与阿特克斯形成一个复合体,以将素H3.3沉积到异性染色中.
- 了解Daxx的体内功能需要剖析其相互作用.
研究的目的:
- 通过创建特定的相互作用突变体来研究Daxx的体内功能.
- 要区分Daxx的Atrx依赖和H3.3依赖的函数.
- 阐明Daxx在表观遗传调节和基因组稳定中的作用.
主要方法:
- 产生两种小鼠达克斯突变基因:达克斯Y130A (取消达克斯-阿特克斯相互作用) 和达克斯S226A (取消达克斯-H3.3相互作用).
- 突变小鼠的生存能力和生育能力评估.
- 胚胎组织的转录组分析,以评估基因表达变化.
- 对内源性逆转录病毒表达和免疫细胞组成的分析.
主要成果:
- 消除了达克斯-阿特克斯相互作用 (DaxxY130A) 的小鼠是可行的和肥沃的,但表现出失调的内源逆转录病毒表达.
- 消除了达克斯-H3.3相互作用的小鼠 (DaxxS226A) 对于产后活力至关重要,这表明它们在胚胎发生后的发育中起着关键作用.
- 达克斯-H3.3相互作用对于静止内源逆转录病毒和维持适当的免疫细胞组成至关重要.
结论:
- 在体内,Daxx表现出Atrx依赖和独立的功能.
- 达克斯-阿特克斯相互作用是不可或缺的生存能力,但影响逆转录病毒沉默.
- 达克斯-H3.3相互作用对于产后存活,逆转录病毒沉默和免疫恒常性至关重要,突出了在表观遗传调节中的不同作用.
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