在多能干细胞中无需TRF2介导的端粒保护
Marta Markiewicz-Potoczny1, Anastasia Lobanova2, Anisha M Loeb1
1Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA.
Nature
|November 26, 2020
概括
对于小鼠胚胎干细胞的存活,特洛米尔保护蛋白TRF2并非必不可少. 缺乏TRF2的细胞避免DNA损伤和染色体融合,显示出独特的发育反应.
科学领域:
- 遗传学
- 细胞生物学
- 发育生物学
背景情况:
- 端粒保护蛋白TRF2对于哺乳动物的基因组完整性至关重要.
- 在大多数细胞类型中,TRF2 枯竭通常会导致染色体融合.
研究的目的:
- 研究TRF2在小鼠胚胎干细胞中的作用.
- 描述TRF2缺乏ES细胞中的DNA损伤反应和端粒稳定性.
主要方法:
- 使用CRISPR-Cas9淘汰查,以确定TRF2-零ES细胞反应中的因素.
- 在端粒上分析DNA损伤标记物 (γH2AX,53BP1).
- 评估ZSCAN4表达及其在端粒保护中的作用.
主要成果:
- 对于小鼠ES细胞的增殖和存活,TRF2是不可缺少的.
- 没有TRF2的ES细胞在端粒上表现出沉默的DNA损伤反应,缺乏53BP1的招募.
- 确定了对POT1B和BRD2的依赖性;它们与TRF2的共同消耗恢复了正规的DNA损伤反应和端粒融合.
- TRF2 枯竭诱导了一个类似于全能体的转录程序,包括ZSCAN4 的上调.
- 上调的ZSCAN4有助于TRF2缺乏ES细胞的端粒保护.
结论:
- 鼠标ES细胞表现出独特的TRF2独立的端粒保护机制.
- 这种机制涉及对DNA损伤的响应和ZSCAN4依赖的转录程序的激活.
- 这些发现揭示了早期发育中的端粒维护和基因组稳定性的新见解.
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