NUP98和RAE1通过HDAC依赖的染色质向性来维持原生细胞功能,以逃避核细胞局部化
Amy E Neely1, Laura A Blumensaadt1, Patric J Ho1
1Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Communications biology
|June 23, 2023
概括
核孔蛋白NUP98和RAE1对于表皮原体的维护至关重要. 它们的枯竭会通过抑制增殖和促进分化而损害组织再生,从而揭示了原始细胞功能的一个关键途径.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 自我更新的体组织依赖于前代细胞进行持续的再生.
- 精确的基因调节网络,规范祖先的功能还没有完全阐明.
研究的目的:
- 调查NUP98和RAE1在维持表皮原生细胞功能中的作用.
- 阐明NUP98和RAE1对组织再生的贡献背后的分子机制.
主要方法:
- 对表皮原体NUP98和RAE1表达的分析.
- 功能性研究涉及降低NUP98或RAE1水平.
- 染色体免疫沉和基因表达分析.
- 评估原生细胞的增殖,分化和再生能力.
- 研究HDAC抑制对NUP98/RAE1局部化和功能的影响.
主要成果:
- NUP98和RAE1在表皮原体中高度表达,并形成核等离子体复合体.
- 耗尽NUP98或RAE1会损害原生细胞的再生能力,抑制繁殖并诱导过早的分化.
- NUP98与表观遗传调节剂 (DNMT1,UHRF1,EZH2) 的转录起点附近的染色质结合,维持它们的表达.
- HDAC1与NUP98的结合部位共占;HDAC抑制减少了NUP98的染色体结合,并破坏了基因表达的调节.
- 抑制HDAC会导致NUP98和RAE1局部化到核中.
结论:
- NUP98和RAE1对于维持表皮原体功能和组织再生至关重要.
- HDAC活动对于将NUP98和RAE1引导到染色质来调节关键表观遗传调节器至关重要.
- 这种途径通过控制表观遗传景观和防止异常核定位来确保祖先的维持.
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